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Qi J, Chen J, von Stillfried S, Kozcera P, Shi Y, Rix A, Kiessling F. Molecular Ultrasound Imaging With Clinically Translatable cRGD-Coated Microbubbles to Assess α v β 3 -Integrin Expression in Inflammatory Bowel Disease. Invest Radiol 2025; 60:407-413. [PMID: 39609095 DOI: 10.1097/rli.0000000000001143] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2024]
Abstract
OBJECTIVES Inflammatory bowel disease (IBD) subdivides into Crohn disease (CD) and ulcerative colitis (UC), and is characterized by unpredictable periods of inflammation and results in significant patient suffering and even death. Conventional diagnostic methods, for example, colonoscopy, computed tomography, or magnetic resonance imaging, have limitations such as invasiveness, patient discomfort, and limited sensitivity and accuracy. Therefore, we propose ultrasound molecular imaging (USMI) to detect and characterize IBD. First, we evaluated integrin-α v β 3 as a biomarker of IBD in human samples and then used clinically translatable cyclic Arg-Gly-Asp-D-Phe-Lys (cRGDfK)-coupled poly(butyl)cyanoacrylate microbubbles (cRGD-MB) to assess IBD in mice. MATERIALS AND METHODS Vascular integrin-α v β 3 expression in human colon tissue samples (healthy, CD and UC, n = 10 per group) was analyzed by immunofluorescence staining. In mice, acute colitis was induced by administration of 4% dextran sodium sulfate in drinking water for 5 days. On day 7, USMI with cRGD-MB was performed in colitis (n = 6) and healthy (n = 5) mice. The signal of bound cRGD-MB was assessed by the destruction-replenishment method. Ex vivo analysis of mouse colon tissue was performed to assess the degree of colitis by hematoxylin-eosin staining and the vascular expression of integrin-α v by immunofluorescence. RESULTS Human samples showed a significantly higher vascular integrin-α v β 3 expression in CD and UC tissue, when compared with healthy samples ( P < 0.005). In mice, a higher binding of cRGD-MB to inflamed colon was detected by USMI compared with healthy controls ( P < 0.005). Immunofluorescence staining confirmed these findings, showing stronger integrin-α v expression in acute colitis, with a good correlation between USMI signal intensity and integrin-α v expression ( r = 0.8, P = 0.0016). CONCLUSIONS Integrin-α v β 3 on vessels is a suitable marker for IBD. USMI using cRGD-MB accurately detects this marker and correlates well with histology. These encouraging results support clinical translation of this imaging method as a noninvasive and cost-effective monitoring tool.
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Affiliation(s)
- Jinwei Qi
- From the Institute for Experimental Molecular Imaging, Medical Faculty, RWTH Aachen University, Aachen, Germany (J.Q., J.C., P.K., Y.S., A.R., F.K.); and Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany (S.V.)
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Hutchings MC, Bateman AC. Nancy histological index in ulcerative colitis: an interobserver study. J Clin Pathol 2025:jcp-2025-210129. [PMID: 40280743 DOI: 10.1136/jcp-2025-210129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2025] [Accepted: 04/13/2025] [Indexed: 04/29/2025]
Abstract
The Nancy histological index (NHI) is a measure of disease activity within colorectal biopsies and a predictor of clinical outcome in ulcerative colitis (UC). We measured interobserver agreement (IOA) during NHI scoring of 20 colorectal biopsies in UC by 13 pathologists of varying grade and experience. The level of IOA was measured using Fleiss' kappa statistic. The degree of IOA was moderate, with kappa scores of 0.53 (SE 0.01) for the whole group (n=13), 0.50 (SE 0.05) for the consultants (n=4) and 0.54 (SE 0.019) for the trainees (n=9). Normal biopsies or those showing a mild increase in lamina propria chronic inflammation were graded most reproducibly. Subjectivity existed at NHI grade boundaries, particularly identification of mild acute inflammation (AI), assessment of AI severity and identification of ulceration. An education programme for pathologists or an artificial intelligence tool may improve IOA in the future.
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Affiliation(s)
- Melissa C Hutchings
- Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
| | - Adrian C Bateman
- Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, UK
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Parra-Izquierdo V, Otero-Regino W, Juliao-Baños F, Frías-Ordoñez JS, Ibañez-Pinilla E, Gil-Parada FL, Marulanda-Fernández H, Otero-Parra L, Otero-Ramos E, Puentes-Manosalva FE, Guzmán Rojas GA, Ernest-Suárez K, Villa-Ovalles K, Paredes-Mendez JE, Jara-Alba ML, Andrade-Zamora D, Ardila-Báez MA, Flórez-Sarmiento C, Veitia G, Sánchez A, Arango-Molano LA, Fluxa F, Freitas Queiroz NS, Serrano M. Dysplasia and Colorectal Cancer Surveillance in Ulcerative Colitis Patients in Latin America: Real-World Data. CROHN'S & COLITIS 360 2025; 7:otae081. [PMID: 39834355 PMCID: PMC11744193 DOI: 10.1093/crocol/otae081] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Indexed: 01/22/2025] Open
Abstract
Background The prevalence of colorectal cancer (CRC) in patients with ulcerative colitis (UC) is higher than in the general population, in Latin America there is a progressive increase of UC, and information about CRC screening in inflammatory bowel disease (IBD) is scarce. The aim of this study was to analyze the findings of endoscopic surveillance of CRC in patients with IBD according to available technology. Methods Multicenter, cross-sectional, analytical study conducted in Latin American countries, in patients with UC, predominantly with more than 8 years of diagnosis and different degrees of disease activity. Surveillance colonoscopies were performed according to available technology. Risk factors for dysplasia detection were analyzed. Results One hundred and forty-four patients, 55.5% women, mean age 47.3 (range 17.1 to 90; SD 15.64) years and mean duration of disease 12.71 (range 0.64 to 57.13; SD 8.08) years. Forty-nine lesions were identified, 18 corresponded to dysplasia. The detection rate of dysplasia per lesion and per procedure was 36.7% and 12.5%, respectively. By logistic regression analysis, the duration of disease (OR 1.12;95%CI:1.047 to 1.215, P = .002) and the presence of post-inflammatory polyps (OR 3.4;95%CI:1.11 to 10.36, P = .031) were risk factors for higher detection of dysplasia. Digital chromoendoscopy was associated with greater detection of dysplasia (OR 4.99, 95%CI: 1.092 to 22.864, P = .038). Conclusions In our region, the duration of disease and the presence of post-inflammatory polyps were the factors with the highest association for dysplasia detection, and digital chromoendoscopy with directed biopsies was the technique of choice. The implementation of a specific surveillance program in colonoscopy in IBD is an effective strategy to achieve high detection rates.
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Affiliation(s)
- Viviana Parra-Izquierdo
- Gastroenterology and Rheumatology, International Hospital of Colombia, Bucaramanga, Colombia
- Cellular and Molecular Immunology Group (INMUBO), Universidad El Bosque, Bogotá, Colombia
| | - William Otero-Regino
- Gastroenterology, National University of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, National University Hospital of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, Gastroenterology and Endoscopy Center, Bogota, Colombia
| | | | - Juan Sebastián Frías-Ordoñez
- Gastroenterology, National University of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, National University Hospital of Colombia, Bogota, Colombia
| | | | | | - Hernando Marulanda-Fernández
- Gastroenterology, National University of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, National University Hospital of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, Gastroenterology and Endoscopy Center, Bogota, Colombia
- Central Police Hospital, Bogota, Colombia
| | - Lina Otero-Parra
- Gastroenterology, National University of Colombia, Bogota, Colombia
- Gastroenterology and Digestive Endoscopy, Gastroenterology and Endoscopy Center, Bogota, Colombia
| | - Elder Otero-Ramos
- Gastroenterology and Digestive Endoscopy, Gastroenterology and Endoscopy Center, Bogota, Colombia
- Central Police Hospital, Bogota, Colombia
| | | | - Gerardo Andrés Guzmán Rojas
- Gastroenterology, Farallones Clinic, Cali, Valle del Cauca, Colombia
- Gastroenterology, Colsanitas Chipi Chape Medical Center Cali, Valle del Cauca, Colombia
| | - Kenneth Ernest-Suárez
- School of Medicine, University of Costa Rica, San José, Costa Rica
- Inflammatory Bowel Disease Unit, Hospital México, Caja Costarricense de Seguro Social, San José, Costa Rica
| | - Keyla Villa-Ovalles
- Gastroenterology and Digestive Endoscopy, Hospital Luis E Aybar, Santo Domingo, Dominican Republic
| | - Juan Eloy Paredes-Mendez
- Gastroenterology, Guillermo Almenara National Hospital, Lima, Perú
- Gastroenterology, International Clinic, Lima, Peru
| | | | - David Andrade-Zamora
- Gastroenterology, Hospital of the Ecuadorian Institute of Social Security of Cuenca, Cuenca, Ecuador
| | | | - Cristian Flórez-Sarmiento
- Cellular and Molecular Immunology Group (INMUBO), Universidad El Bosque, Bogotá, Colombia
- Gastroenterology, Hospital Internacional de Colombia, Bucaramanga, Colombia
| | - Guillermo Veitia
- Gastroenterology, Hospital Vargas de Caracas, Caracas, Venezuela
- Gastroenterology, Universidad Central de Venezuela, Caracas, Venezuela
| | - Abel Sánchez
- Gastroenterology and Digestive Endoscopy, Roosevelt Hospital, Guatemala City. Guatemala
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Di Vincenzo F, Quintero MA, Serigado JM, Koru-Sengul T, Killian RM, Poveda J, England J, Damas O, Kerman D, Deshpande A, Abreu MT. Histologic and Endoscopic Findings Are Highly Correlated in a Prospective Cohort of Patients With Inflammatory Bowel Diseases. J Crohns Colitis 2024:jjae141. [PMID: 39739605 DOI: 10.1093/ecco-jcc/jjae141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2024] [Revised: 07/23/2024] [Accepted: 12/06/2024] [Indexed: 01/02/2025]
Abstract
BACKGROUND AND AIMS The advantages of endoscopic vs histologic assessments of inflammation in inflammatory bowel disease remain unclear. We compared endoscopic and histologic inflammation in a prospective cohort. Furthermore, in patients with discordant findings, we compared the ability of endoscopy vs histology to predict disease course. METHODS Ulcerative colitis (UC) or Crohn's disease (CD) patients underwent routine colonoscopies with intestinal biopsies, which included ratings of inflammation severity. Tetrachoric correlation analysis between the endoscopic and histologic inflammation ratings was performed. In postsurgical CD patients, major adverse outcomes (MAOs) were recorded. RESULTS The analysis included 749 patients (60.2% CD patients), with 2807 biopsied segments. We found high concordance between endoscopist and pathologist inflammation ratings (0.84, 95% confidence interval, 0.81-0.87, p < 0.0001). Only 12.5% of biopsied segments exhibited microscopic inflammation without endoscopic inflammation. Neo-terminal ileum (neo-TI) biopsies exhibited the highest discordance; UC colonic biopsies had the highest concordance. Postsurgical CD patients who completed the 48-month follow-up (n = 138) were included in the survival analysis. The probability of MAO-free survival was significantly higher in patients with a Rutgeerts score of i0 at baseline than in those with higher scores. Microscopic inflammation in the neo-TI did not predict a higher risk of MAOs (p = 1.00). CONCLUSIONS In a real-world setting, endoscopic inflammation predicted histologic inflammation with high accuracy. In patients with a Rutgeerts score of i0, microscopic inflammation in neo-TI biopsies did not predict more aggressive disease behavior over the next 4 years. These results have implications for the design of clinical trials, suggesting the use of endoscopic healing as an endpoint.
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Affiliation(s)
- Federica Di Vincenzo
- Division of Gastroenterology, Department of Medicine, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario "A. Gemelli", IRCCS, Rome, Italy
| | - Maria A Quintero
- Division of Gastroenterology, Department of Medicine, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
| | - Joao M Serigado
- Department of Gastroenterology, Hepatology, and Nutrition, Martin North Hospital, Cleveland Clinic, Stuart, FL, USA
| | - Tulay Koru-Sengul
- Department of Public Health Sciences, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
| | - Rose Marie Killian
- John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA
| | - Julio Poveda
- Department of Pathology, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
| | - Jonathan England
- Department of Pathology, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
| | - Oriana Damas
- Division of Gastroenterology, Department of Medicine, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
| | - David Kerman
- Division of Gastroenterology, Department of Medicine, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
| | - Amar Deshpande
- Division of Gastroenterology, Department of Medicine, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
| | - Maria T Abreu
- Division of Gastroenterology, Department of Medicine, University of Miami - Leonard Miller School of Medicine, Miami, FL, USA
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Cai C, Shi Q, Li J, Jiao Y, Xu A, Zhou Y, Wang X, Peng C, Zhang X, Cui X, Chen J, Xu J, Sun Q. Pathologist-level diagnosis of ulcerative colitis inflammatory activity level using an automated histological grading method. Int J Med Inform 2024; 192:105648. [PMID: 39396418 DOI: 10.1016/j.ijmedinf.2024.105648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2024] [Revised: 09/18/2024] [Accepted: 10/06/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND AND AIMS Inflammatory bowel disease (IBD) is a global disease that is evolving with increasing incidence. However, there are few works on computationally assisted diagnosis of IBD based on pathological images. Therefore, based on the UK and Chinese IBD diagnostic guidelines, our study established an artificial intelligence-assisted diagnostic system for histologic grading of inflammatory activity in ulcerative colitis (UC). METHODS We proposed an efficient deep-learning (DL) method for grading inflammatory activity in whole-slide images (WSIs) of UC pathology. Our model was constructed using 603 UC WSIs from Nanjing Drum Tower Hospital for model train set and internal test set. We collected 212 UC WSIs from Zhujiang Hospital as an external test set. Initially, the pre-trained ResNet50 model on the ImageNet dataset was employed to extract image patch features from UC patients. Subsequently, a multi-instance learning (MIL) approach with embedded self-attention was utilized to aggregate tissue image patch features, representing the entire WSI. Finally, the model was trained based on the aggregated features and WSI annotations provided by senior gastrointestinal pathologists to predict the level of inflammatory activity in UC WSIs. RESULTS In the task of distinguishing the presence or absence of inflammatory activity, the Area Under Curve (AUC) value in the internal test set is 0.863 (95% confidence interval [CI] 0.829, 0.898), with a sensitivity of 0.913 (95% [CI] 0.866, 0.961), and specificity of 0.816 (95% [CI] 0.771, 0.861). The AUC in the external test set is 0.947 (95% confidence interval [CI] 0.939, 0.955), with a sensitivity of 0.889 (905% [CI] 0.837, 0.940), and specificity of 0.858 (95% [CI] 0.777, 0.939). For distinguishing different levels of inflammatory activity in UC, the average Macro-AUC in the internal test set and the external test set are 0.827 (95% [CI] 0.803, 0.850) and 0.908 (95% [CI] 0.882, 0.935). the average Micro-AUC in the internal test set and the external test set are 0.816 (95% [CI] 0.792, 0.840) and 0.898 (95% [CI] 0.869, 0.926). CONCLUSIONS Comparative analysis with diagnoses made by pathologists at different expertise levels revealed that the algorithm reached a proficiency comparable to the pathologist with 5 years of experience. Furthermore, our algorithm performed superior to other MIL algorithms.
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Affiliation(s)
- Chengfei Cai
- School of Automation, Nanjing University of Information Science and Technology, Nanjing 21004, Jiangsu Province, China; Jiangsu Key Laboratory of Intelligent Medical Image Computing, School of Future Technology, Nanjing University of Information Science and Technology, Nanjing 21004, Jiangsu Province, China; College of Information Engineering, Taizhou University, Taizhou 225300, Jiangsu Province, China
| | - Qianyun Shi
- Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Jun Li
- Jiangsu Key Laboratory of Intelligent Medical Image Computing, School of Future Technology, Nanjing University of Information Science and Technology, Nanjing 21004, Jiangsu Province, China
| | - Yiping Jiao
- Jiangsu Key Laboratory of Intelligent Medical Image Computing, School of Future Technology, Nanjing University of Information Science and Technology, Nanjing 21004, Jiangsu Province, China
| | - Andi Xu
- Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Yangshu Zhou
- Department of Pathology, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, Guangdong Province, China
| | - Xiangxue Wang
- Jiangsu Key Laboratory of Intelligent Medical Image Computing, School of Future Technology, Nanjing University of Information Science and Technology, Nanjing 21004, Jiangsu Province, China
| | - Chunyan Peng
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Xiaoqi Zhang
- Department of Gastroenterology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Xiaobin Cui
- Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Jun Chen
- Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
| | - Jun Xu
- Jiangsu Key Laboratory of Intelligent Medical Image Computing, School of Future Technology, Nanjing University of Information Science and Technology, Nanjing 21004, Jiangsu Province, China.
| | - Qi Sun
- Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China; Center for Digestive Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
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Rubio CA, Lang‐Schwarz C, Vieth M. Architectural crypt distortions in ulcerative colitis: Time for reappraisal. J Gastroenterol Hepatol 2024; 39:2479-2486. [PMID: 39522510 PMCID: PMC11660196 DOI: 10.1111/jgh.16811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 10/22/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024]
Abstract
Chronic mucosal inflammation and architectural crypt distortions (ACD) are essential for the histologic diagnosis of ulcerative colitis (UC). ACD in UC has been defined as irregularly arranged, dilated, branched, and shortened crypts with inequality of inter-crypt distance. However, neither the diagnostic sections' crypt phenotype nor the cutting mode have been considered. In this regard, previous studies showed that most diagnostic biopsies in UC are fortuitously crosscut at laboratories. In this communication, we review the crypt phenotypes that are included in the ACD in UC notion: crypts in asymmetric branching, crypt rings in tandem, crypts with lateral buds, face-to-face "kissing crypts," crypts-in-crypts, laterally orientated crypts in anthemia fold domains, and crypts with irregular shape and size in innominate groves domains. The awareness that disparate crypt phenotypes may participate in the ACD notion may open new vistas in the interpretation of crypt distortions in crosscut diagnostic sections in UC. The present findings will permit endoscopists and clinicians to better understand the narrative of ACD in the pathological diagnosis.
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Affiliation(s)
- Carlos A Rubio
- Department of Oncology and PathologyKarolinska Institute and University HospitalStockholmSweden
| | - Corinna Lang‐Schwarz
- Institute of PathologyFriedrich‐Alexander‐Universität Erlangen‐Nürnberg, Klinikum BayreuthBayreuthGermany
| | - Michael Vieth
- Institute of PathologyFriedrich‐Alexander‐Universität Erlangen‐Nürnberg, Klinikum BayreuthBayreuthGermany
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Hall R, Patel K, Poullis A, Pollok R, Honap S. Separating Infectious Proctitis from Inflammatory Bowel Disease-A Common Clinical Conundrum. Microorganisms 2024; 12:2395. [PMID: 39770599 PMCID: PMC11678827 DOI: 10.3390/microorganisms12122395] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 01/11/2025] Open
Abstract
Proctitis refers to inflammation in the rectum and may result in rectal bleeding, discharge, urgency, tenesmus, and lower abdominal pain. It is a common presentation, particularly in genitourinary medicine and gastroenterology, as the two most common causes are sexually transmitted infections and inflammatory bowel disease. The incidence of infective proctitis is rising, particularly amongst high-risk groups, including men who have sex with men, those with HIV seropositive status, and those participating in high-risk sexual behaviours. The most commonly isolated organisms are Neisseria gonorrhoeae, Chlamydia trachomatis, Treponema palladium, herpes simplex virus, and Mycoplasma genitalium. Recently, proctitis was also identified as a common feature during the Mpox outbreak. Distinguishing infective proctitis from inflammatory bowel disease remains a significant clinical challenge as there is significant overlap in the clinical presentation and their endoscopic and histological features. This review compares and highlights the distinguishing hallmarks of both inflammatory and infective causes of proctitis. It provides a practical guide to describe the key features that clinicians should focus on in both clinical and key diagnostic investigations to avoid potential misdiagnosis.
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Affiliation(s)
- Richard Hall
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
| | - Kamal Patel
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
| | - Andrew Poullis
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
| | - Richard Pollok
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
- Institute of Infection and Immunity, St George’s University, London SW17 0RE, UK
| | - Sailish Honap
- Department of Gastroenterology, St George’s University Hospital, London SW17 0QT, UK; (R.H.)
- School of Immunology and Microbial Sciences, King’s College London, London SE1 9NH, UK
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Fiorillo M, Neri B, Mancone R, Russo C, Iacobini F, Schiavone SC, De Cristofaro E, Migliozzi S, Exacoustos C, Biancone L. Inflammatory Bowel Disease and Endometriosis: Diagnosis and Clinical Characteristics. Biomedicines 2024; 12:2521. [PMID: 39595086 PMCID: PMC11592220 DOI: 10.3390/biomedicines12112521] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/28/2024] Open
Abstract
Background/Objectives: Endometriosis and inflammatory bowel disease (IBD) share some epidemiological, clinical and pathogenetic features. A differential diagnosis between pelvic endometriosis and IBD may be challenging, even for expert clinicians. In the present review, we aimed to summarize the currently available data regarding the relationship between endometriosis and IBD and their possible association. Methods: The PubMed and Scopus database were considered, by searching the following terms: "Crohn's Disease", "Ulcerative Colitis", "Endometriosis", "Adenomyosis", and "Inflammatory Bowel Disease", individually or combined. Full-text papers published in English with no date restriction were considered. Results: Few studies have researched the possible association between endometriosis and IBD. Both conditions are characterized by chronic recurrent symptoms, which may be shared (abdominal pain, fatigue, infertility, menstrual irregularities, diarrhea, constipation). Deep infiltrating endometriosis (DIE) can cause bowel symptoms. In a large Danish study, a 50% increased risk of IBD was observed in women with endometriosis. A missed diagnosis of endometriosis and an increased risk of endometriosis has been reported in IBD. Current evidence does not support an association between endometriosis and IBD characteristics. However, IBD may be associated with DIE, characterized by pelvic symptoms (dyschezia, dyspareunia). Preliminary observations suggest an increased IBD risk in patients with endometriosis treated with hormonal therapy. Conclusions: Current findings suggest that a careful search is needed for concomitant endometriosis in subgroups of patients with IBD showing compatible symptoms and vice versa. A multidisciplinary approach including dedicated gastroenterologists and gynecologists is required for a proper search for IBD and endometriosis in subgroups of patients. This approach may avoid diagnostic delays or overtreatments for these conditions.
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Affiliation(s)
- Mariasofia Fiorillo
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Benedetto Neri
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
- Therapeutic GI Endoscopy Unit, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy
| | - Roberto Mancone
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Consuelo Russo
- Obstetrics and Gynecological Unit, Department of Surgical Sciences, University “Tor Vergata” of Rome, 00133 Rome, Italy; (C.R.); (F.I.); (C.E.)
- Department of Women, Children, and Public Health Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy
| | - Federica Iacobini
- Obstetrics and Gynecological Unit, Department of Surgical Sciences, University “Tor Vergata” of Rome, 00133 Rome, Italy; (C.R.); (F.I.); (C.E.)
| | - Sara Concetta Schiavone
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Elena De Cristofaro
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Stefano Migliozzi
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
| | - Caterina Exacoustos
- Obstetrics and Gynecological Unit, Department of Surgical Sciences, University “Tor Vergata” of Rome, 00133 Rome, Italy; (C.R.); (F.I.); (C.E.)
| | - Livia Biancone
- Gastroenterological Unit, Department of Systems Medicine, University “Tor Vergata” of Rome, 00133 Roma, Italy; (M.F.); (B.N.); (R.M.); (S.C.S.); (E.D.C.); (S.M.)
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Samolygo IS, Aminova AI, Yeryushova TY, Matsukatova BO, Andrianova KA, Gundina AV, Erdes SI. Unusual onset and course of Crohn’s disease in children. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2024:221-224. [DOI: 10.31146/1682-8658-ecg-226-6-221-224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
The purpose of the article is to demonstrate a clinical case of Crohn’s disease in an 8-year-old child. Materials and methods: The given clinical example is a case of a non-classical variant of the course of Crohn’s disease in an 8-year-old child who debuted with an upper respiratory tract lesion in combination with abdominal pain against the background of long courses of antibacterial therapy. Conclusion: This clinical case demonstrates the complexity of the diagnostic search, the need for careful history collection and differential diagnosis.
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Affiliation(s)
- I. S. Samolygo
- I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. I. Aminova
- I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | - T. Yu. Yeryushova
- I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | - B. O. Matsukatova
- I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | - K. A. Andrianova
- I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. V. Gundina
- I. M. Sechenov First Moscow State Medical University (Sechenov University)
| | - S. I. Erdes
- I. M. Sechenov First Moscow State Medical University (Sechenov University)
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10
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Baidoo N, Sanger GJ. Age-related decline in goblet cell numbers and mucin content of the human colon: Implications for lower bowel functions in the elderly. Exp Mol Pathol 2024; 139:104923. [PMID: 39154390 DOI: 10.1016/j.yexmp.2024.104923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 08/20/2024]
Abstract
BACKGROUND & AIMS Older people experience a greater incidence of lower bowel disorders, including constipation. Causes can include factors associated with growing older, such as use of medications or disease, but compounded by degenerative changes within the bowel wall. It has been suggested that the latter is exacerbated by loss of an effective mucosal barrier to luminal contents. In human colon, little is known about the impact of ageing on key components of this barrier, namely the goblet cells and mucin content. METHODS Changes in the number of goblet cells and density of mucin content were investigated in macroscopically normal human ascending (AC; n = 13) and descending (DC; n = 14) colon from elderly (≥ 67 years) and younger adults (60 years and below). Samples were serially sectioned and stained for haematoxylin and eosin to assess tissue morphology, and alcian blue periodic acid Schiff (ABPAS) and MUC-2 antibody to identify goblet cells producing mucins. New procedures in visualization and identification of goblet cells and mucin contents were employed to ensure unbiased counting and densitometric analysis. RESULTS Compared with the younger adults, the numbers of goblet cells per crypt were significantly lower in the elderly AC (72 ± 1.2 vs 51 ± 0.5) and DC (75 ± 2.6 vs. 54 ± 1.9), although this reduction did not reach statistical significance when assessed per mucosal area (AC: P = 0.068; DC: P = 0.096). In both regions from the elderly, numerous empty vesicles (normally containing mucins) were observed, and some areas of epithelium were devoid of goblet cells. Thus, the density of mucin content per unit mucosal area were significantly reduced with age. CONCLUSIONS Ageing could result in a reduced number of goblet cells and development of degenerative changes in mucin production. Together, these have implications for the mucus barrier function in the colon of elderly individuals.
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Affiliation(s)
- Nicholas Baidoo
- University of Westminster, School of Life Sciences. New Cavendish Street, UK; Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK.
| | - Gareth J Sanger
- Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
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11
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Feakins RM. Inflammatory disorders of the large intestine. MORSON AND DAWSON'S GASTROINTESTINAL PATHOLOGY 2024:709-857. [DOI: 10.1002/9781119423195.ch35] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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12
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Cicerone C, D’Amico F, Allocca M, Zilli A, Parigi TL, Danese S, Furfaro F. A Comprehensive Multidisciplinary Approach to Diagnosing Chronic Inflammatory Bowel Diseases: Integration of Clinical, Endoscopic, and Imaging Modalities. Diagnostics (Basel) 2024; 14:1530. [PMID: 39061667 PMCID: PMC11275644 DOI: 10.3390/diagnostics14141530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Revised: 07/12/2024] [Accepted: 07/13/2024] [Indexed: 07/28/2024] Open
Abstract
Chronic inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, present diagnostic challenges due to their complex and heterogeneous nature. While histology remains fundamental for accurate diagnosis, a multidisciplinary approach incorporating clinical, endoscopic, and imaging modalities is increasingly recognized as essential for comprehensive evaluation. This article delves into the importance of integrating various diagnostic techniques in the assessment of IBD. Colonoscopy and histology, with its ability to directly visualize the intestinal mucosa, play a central role in the diagnostic process. However, histological analysis alone may not suffice, necessitating the inclusion of advanced imaging techniques, such as magnetic resonance enterography (MRE), computed tomography enterography (CTE), and intestinal ultrasound (IUS). These techniques provide valuable insights into the disease's extent, severity, and complications, and should be used in conjunction with biochemical parameters. These modalities complement traditional endoscopic and histological findings, offering a more holistic understanding of the disease process. A multidisciplinary approach that incorporates clinical, endoscopic, histological, serological, and imaging assessments enables clinicians to achieve a more accurate and timely diagnosis of IBD. Moreover, this integrated approach facilitates personalized treatment strategies tailored to individual patient needs, ultimately improving clinical outcomes and quality of life for those affected by chronic inflammatory bowel diseases.
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Affiliation(s)
- Clelia Cicerone
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Ferdinando D’Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
- Department of Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, 20132 Milan, Italy; (C.C.); (F.D.); (M.A.); (A.Z.); (T.L.P.); (S.D.)
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13
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Laterza L, Piscaglia AC, Bibbò S, Arena V, Brisigotti M, Fabbretti G, Stefanelli ML, Cesario V, Maresca R, Poscia A, Pugliese D, Gaetani E, Papa A, Cammarota G, Armuzzi A, Gasbarrini A, Scaldaferri F. Histologic Disease Persists beyond Mucosal Healing and Could Predict Reactivation in Ulcerative Colitis. J Pers Med 2024; 14:505. [PMID: 38793087 PMCID: PMC11122403 DOI: 10.3390/jpm14050505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/01/2024] [Accepted: 05/06/2024] [Indexed: 05/26/2024] Open
Abstract
Mucosal healing (MH) is the main target in ulcerative colitis (UC) treatment. Even if MH lowers the risk of disease reactivation, some patients still relapse. Histologic activity (HA) beyond MH could explain these cases. This study aims to assess how many patients with MH have HA and which lesions are associated with relapse. We retrospectively enrolled UC patients showing MH, expressed as a Mayo Endoscopic Subscore (MES) of 0 and 1 upon colonoscopy. We reviewed the histological reports of biopsies evaluating the presence of typical lesions of UC and assessed the number of clinical relapses after 12 months. Among 100 enrolled patients, 2 showed no histological lesions. According to univariate analysis, patients with a higher number of histological lesions at the baseline had a higher risk of relapse (OR 1.25, p = 0.012), as well as patients with basal plasmacytosis (OR 4.33, p = 0.005), lamina propria eosinophils (OR 2.99, p = 0.047), and surface irregularity (OR 4.70, p = 0.010). However, in the multivariate analysis, only basal plasmacytosis (OR 2.98, p = 0.050) and surface irregularity (OR 4.50, p = 0.024) were confirmed as risk factors for disease reactivation. HA persists in a significant percentage of patients with MH. Despite the presence of MH, patients with basal plasmacytosis and surface irregularity have a higher risk of relapse.
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Affiliation(s)
- Lucrezia Laterza
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
| | | | - Stefano Bibbò
- UOC di Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
| | - Vincenzo Arena
- Istituto di Anatomia Patologica, Dipartimento Scienze della Salute della Donna, del Bambino e di Sanità Pubblica-Area Anatomia Patologica, Fondazione Policlinico Universitario “A.Gemelli” IRCCS, 00168 Rome, Italy
| | | | | | | | - Valentina Cesario
- Endoscopy and Gastroenterology Unit, State Hospital, 47893 Cailungo, San Marino
| | - Rossella Maresca
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Andrea Poscia
- UOC ISP Prevention and Surveillance of Infectious and Chronic Diseases, Department of Prevention, Local Health Authority (ASUR-AV2), 60035 Jesi, Italy
| | - Daniela Pugliese
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
| | - Eleonora Gaetani
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Alfredo Papa
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Giovanni Cammarota
- UOC di Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, 00168 Rome, Italy
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | | | - Antonio Gasbarrini
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
| | - Franco Scaldaferri
- Centro per le Malattie dell’Apparato Digerente (CEMAD), Digestive Disease Center, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy (F.S.)
- Dipartimento di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
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14
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Leoncini G, Reggiani-Bonetti L, Simoncelli G, Villanacci V. Histology of IBD and related colitides in the elderly. Minerva Gastroenterol (Torino) 2024; 70:68-78. [PMID: 34278750 DOI: 10.23736/s2724-5985.21.02888-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Inflammatory bowel disease (IBD) are chronic relapsing diseases, affecting both children and adults with a life-long duration. An increased co-morbidity gives raise to fragility in the elderly. In this regard it should consider that several non-IBD colitides may mimic both ulcerative colitis and Crohn's disease. Moreover, chronic diseases represent a clinical challenge, mostly about treatment effectiveness. Finally, it is worth noting that patients with long-standing diseases - and elderly patients among them - have an increased malignancy risk when compared to general (non-IBD) population. Our paper aims to review the three main histological topics that play a role in the clinical management of IBD in the elderly, namely differential diagnosis, mucosal healing and IBD-associated dysplasia.
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Affiliation(s)
- Giuseppe Leoncini
- Unit of Pathology, ASST del Garda, Desenzano del Garda, Brescia, Italy -
| | - Luca Reggiani-Bonetti
- Unit of Pathology, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
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15
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Feakins R, Borralho Nunes P, Driessen A, Gordon IO, Zidar N, Baldin P, Christensen B, Danese S, Herlihy N, Iacucci M, Loughrey MB, Magro F, Mookhoek A, Svrcek M, Rosini F. Definitions of Histological Abnormalities in Inflammatory Bowel Disease: an ECCO Position Paper. J Crohns Colitis 2024; 18:175-191. [PMID: 37607017 PMCID: PMC10896637 DOI: 10.1093/ecco-jcc/jjad142] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2023] [Indexed: 08/24/2023]
Abstract
Histological assessment of endoscopic biopsies in inflammatory bowel disease [IBD] plays an important role in clinical management, investigative studies, and clinical trials. Scoring schemes consisting of multiple histological items and offering considerable precision are widely available. However, definitions of histological abnormalities are often inconsistent. Furthermore, interobserver variability for their recognition and assessment may be high. The European Crohn's and Colitis Organisation [ECCO] formed an expert panel to explore definitions of histological abnormalities in IBD, with the aim of improving the quality of diagnosis and facilitating development of scoring schemes. The process confirmed that the current definitions often have no evidence base and vary between sources. Using available evidence and expert knowledge, the panel produced a series of ECCO consensus position statements on histological features in IBD.
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Affiliation(s)
- Roger Feakins
- Department of Cellular Pathology, Royal Free London NHS Foundation Trust; University College London; London, UK
| | - Paula Borralho Nunes
- Department of Pathology, Hospital Cuf Descobertas, Lisboa and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Ann Driessen
- Department of Pathology, University Hospital Antwerp, University of Antwerp, Edegem, Belgium
| | - Ilyssa O Gordon
- Department of Pathology, Robert J. Tomsich Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Nina Zidar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Pamela Baldin
- Department of Pathology, Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels, Belgium
| | - Britt Christensen
- Royal Melbourne Hospital Melbourne, Department of Gastroenterology, Parkville; University of Melbourne, Department of Medicine, Melbourne, Victoria, Australia
| | - Silvio Danese
- IRCCS Ospedale and University Vita-Salute San Raffaele, Department of Gastroenterology, Milan, Italy
| | - Naoimh Herlihy
- Department of Cellular Pathology, University College London Hospital NHS Foundation Trust, London, UK
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Maurice B Loughrey
- Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast; Department of Cellular Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust;Belfast,UK
| | - Fernando Magro
- CINTESIS@RISE, Faculty of Medicine of the University of Porto, Porto, Portugal
| | - Aart Mookhoek
- Institute of Tissue Medicine and Pathology, University of Bern, Bern, Switzerland
| | - Magali Svrcek
- Sorbonne Université, AP-HP, Hôpital Saint-Antoine, Department of Pathology, Paris, France
| | - Francesca Rosini
- Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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16
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Pavel C, Diculescu MM, Stepan AE, Constantinescu G, Sandru V, Ţieranu CG, Tomescu L, Constantinescu A, Patoni C, Plotogea OM, Ilie M. Considering Histologic Remission in Ulcerative Colitis as a Long-Term Target. J Clin Med 2024; 13:289. [PMID: 38202296 PMCID: PMC10780018 DOI: 10.3390/jcm13010289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 12/17/2023] [Accepted: 12/31/2023] [Indexed: 01/12/2024] Open
Abstract
Monitoring disease activity in inflammatory bowel disease (IBD) is challenging since clinical manifestations do not represent reliable surrogates for an accurate reflection of the inflammatory burden. Endoscopic remission had been the most significant endpoint target in the last years; nevertheless, a remarkable proportion of patients continue to relapse despite a normal-appearing mucosa, highlighting that endoscopy may underestimate the true extent of the disease. A subtle hint of the importance that histology plays in the long-term course of the disease has been endorsed by the STRIDE-II consensus, which recommends considering histologic healing for ulcerative colitis (UC), even though it is not stated to be a compulsory formal target. It is a continuum-changing paradigm, and it is almost a certainty that in the near future, histologic healing may become the new formal target for ulcerative colitis. It must be emphasized that there is great heterogeneity in defining histological remission, and the main criteria or cut-off values for inflammatory markers are still in an ill-defined area. The complexity of some histologic scores is a source of confusion among clinicians and pathologists, leading to low adherence in clinical practice when it comes to a homogenous histopathological report. Therefore, a standardized and more practical approach is urgently needed.
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Affiliation(s)
- Christopher Pavel
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Mircea Mihai Diculescu
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Fundeni Clinical Institute, 022328 Bucharest, Romania
| | - Alex-Emilian Stepan
- Department of Pathology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania;
| | - Gabriel Constantinescu
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Vasile Sandru
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Cristian George Ţieranu
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, “Elias” Emergency University Hospital, 011461 Bucharest, Romania
| | - Luiza Tomescu
- Department of Pathology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania;
- Oncology Institute “Prof. Dr. Alexandru Trestioreanu”, 022328 Bucharest, Romania
| | - Alexandru Constantinescu
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Emergency University Hospital, 050098 Bucharest, Romania
| | - Cristina Patoni
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Central Military Emergency Hospital “Dr. Carol Davila”, 010825 Bucharest, Romania
| | - Oana-Mihaela Plotogea
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
| | - Madalina Ilie
- Department of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, Romania; (C.P.); (M.M.D.); (G.C.); (V.S.); (C.G.Ţ.); (A.C.); (C.P.); (M.I.)
- Department of Gastroenterology, Clinical Emergency Hospital of Bucharest, 014461 Bucharest, Romania
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17
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Pai RK, D'Haens G, Kobayashi T, Sands BE, Travis S, Jairath V, De Hertogh G, Park B, McGinnis K, Redondo I, Lipitz NG, Gibble TH, Magro F. Histologic assessments in ulcerative colitis: the evidence behind a new endpoint in clinical trials. Expert Rev Gastroenterol Hepatol 2024; 18:73-87. [PMID: 38509826 DOI: 10.1080/17474124.2024.2326838] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2023] [Accepted: 03/01/2024] [Indexed: 03/22/2024]
Abstract
INTRODUCTION Treatment goals for ulcerative colitis (UC) are evolving from the achievement of clinical remission to more rigorous goals defined by endoscopic and histologic healing. Achievement of deeper remission targets aims to reduce the risk of colectomy, hospitalizations, and colorectal cancer. AREAS COVERED This review covers histologic assessments, histologic remission as a clinical trial endpoint, and the association between histologic disease activity and clinical outcomes. Future directions are also discussed, including the use of advanced imaging and artificial intelligence technologies, as well as potential future treatment targets beyond histologic remission. EXPERT OPINION Histologic assessments are used for their sensitivity in measuring mucosal inflammatory changes in UC. Due to correlation with disease activity, histologic assessments may support clinical decision-making regarding treatment decisions as such assessments can be associated with rates of clinical relapse, hospitalization, colectomy, and neoplasia. While histologic remission is limited by varying definitions and multiple histologic indices, work is ongoing to create a consensus on the use of histologic assessments in clinical trials. As research advances, aspirational targets beyond histologic remission, such as molecular healing and disease clearance, are being explored.
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Affiliation(s)
- Rish K Pai
- Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ, USA
| | - Geert D'Haens
- Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Amsterdam, Netherlands
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Bruce E Sands
- Dr. Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Simon Travis
- Kennedy Institute and Biomedical Research Centre, University of Oxford, Oxford, UK
| | - Vipul Jairath
- Division of Gastroenterology, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada
| | - Gert De Hertogh
- Department of Pathology, University Hospitals Leuven, Leuven, Belgium
| | - Bomina Park
- Eli Lilly and Company, Indianapolis, IN, USA
| | | | | | | | | | - Fernando Magro
- CINTESIS@RISE, Departmento, Faculty of Medicine of the University of Porto, Porto, Portugal
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18
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Norouzkhani N, Bahari A, Faramarzi M, Shokri Shirvani J, Eslami S, Tabesh H. Development and Validation of an Educational Book on Self-Management in Inflammatory Bowel Disease Based on Patient Preferences and Expert Opinions: A Methodological Study. J Clin Med 2023; 12:7659. [PMID: 38137727 PMCID: PMC10744084 DOI: 10.3390/jcm12247659] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2023] [Revised: 08/03/2023] [Accepted: 08/09/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Self-management education resources for inflammatory bowel disease (IBD) using concepts remain infrequent. We aim to describe the development and evaluation process of educational material for self-management in IBD based on patient preferences and expert opinions. RESEARCH DESIGN AND METHODS The method of this study includes two main phases of development and validation in five steps in the following order: (1) identification of information needs for patients with IBD; (2) content development with a comprehensive literature review and scientific texts related to IBD; (3) measuring the face validity of the content based on the expert opinions in the field of IBD; (4) validation of the content with the experts in the field of IBD; and (5) validation by target audiences. RESULTS The expert panel comprises ten gastroenterologists, nutritionists, psychologists, gynecologists, and nurses. The total suitability score is 79.5%. The final draft version of the educational self-management material was presented to 30 IBD patients who were satisfied (n = 24; 80%) with the material. CONCLUSIONS This study shows the development process and is validated for face and content validity by the academic multidisciplinary expert panel and target group. Patients and their caregivers can use this content to cope with their disease.
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Affiliation(s)
- Narges Norouzkhani
- Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran or (N.N.)
| | - Ali Bahari
- Department of Internal Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran
| | - Mahbobeh Faramarzi
- Population, Family and Spiritual Health Research Center, Health Research Institute, Babol University of Medical Sciences, Babol 47176-47754, Iran;
| | - Javad Shokri Shirvani
- Department of Internal Medicine, Babol University of Medical Sciences, Babol 47176-47754, Iran
| | - Saeid Eslami
- Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran or (N.N.)
- Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran
| | - Hamed Tabesh
- Department of Medical Informatics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad 13944-91388, Iran or (N.N.)
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19
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Rubio CA, Vieth M, Lang-Schwarz C. Novel histological repertoire of crypt-associated anomalies in inflamed colon mucosa. J Clin Pathol 2023; 76:531-535. [PMID: 35273118 PMCID: PMC10423556 DOI: 10.1136/jclinpath-2022-208152] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 02/20/2022] [Indexed: 11/03/2022]
Abstract
AIMS Studying crypt branching in ulcerative colitis (UC) and in infectious colitis (IC), we detected previously unreported crypt-associated anomalies (CAAs). The objective was to describe, illustrate and assess the frequency of CAAs in inflamed colon mucosa in patients with UC and IC. METHODS Sections from 100 consecutive biopsies with UC, in 50 with IC and in 27 with UC in remission (UCR) were reviewed. The following CAAs were identified: crypt eosinophilia, intracryptal epithelial hyperplasia, intracryptal epithelial budding, intracryptal supernumerary crypts, intracryptal epithelial bridges, crypt rings in rows and off-centre epithelial budding. RESULTS The frequency of crypts with extensive crypt eosinophilia and with intracryptal epithelial budding was significantly higher in UC than in IC and UCR (p<0.05); the frequency in the remaining histological parameters was similar in UC, IC and UCR. CONCLUSIONS CAAs were found interspersed with branching crypts. CAAs persisted in long-lasting UC mucosal inflammation, but declined when the inflammation waned. Since similar anomalies are not present in normal colon mucosa, the results suggest that CAAs had been boosted by the ongoing mucosal inflammation. The development of these previously unreported CAAs in the colon mucosa with inflammation might embody pathological aberrations of cryptogenesis.
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Affiliation(s)
- Carlos A Rubio
- Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Corinna Lang-Schwarz
- Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
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20
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Imdad A, Pandit NG, Zaman M, Minkoff NZ, Tanner-Smith EE, Gomez-Duarte OG, Acra S, Nicholson MR. Fecal transplantation for treatment of inflammatory bowel disease. Cochrane Database Syst Rev 2023; 4:CD012774. [PMID: 37094824 PMCID: PMC10133790 DOI: 10.1002/14651858.cd012774.pub3] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2023]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal (GI) tract that is thought to be associated with a complex interplay between the immune system, the GI tract lining, the environment, and the gut microbiome, leading to an abnormal inflammatory response in genetically susceptible individuals. An altered composition of the gut's native microbiota, known as dysbiosis, may have a major role in the pathogenesis of ulcerative colitis (UC) and Crohn disease (CD), two subtypes of IBD. There is growing interest in the correction of this underlying dysbiosis using fecal microbiota transplantation (FMT). OBJECTIVES To evaluate the benefits and safety profile of FMT for treatment of IBD in adults and children versus autologous FMT, placebo, standard medication, or no intervention. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, two clinical trial registries, and the reference sections of published trials through 22 December 2022. SELECTION CRITERIA We included randomized controlled trials that studied adults and children with UC or CD. Eligible intervention arms used FMT, defined as the delivery of healthy donor stool containing gut microbiota to a recipient's GI tract, to treat UC or CD. DATA COLLECTION AND ANALYSIS Two review authors independently screened studies for inclusion. Our primary outcomes were: 1. induction of clinical remission, 2. maintenance of clinical remission, and 3. serious adverse events. Our secondary outcomes were: 4. any adverse events, 5. endoscopic remission, 6. quality of life, 7. clinical response, 8. endoscopic response, 9. withdrawals, 10. inflammatory markers, and 11. microbiome outcomes. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS We included 12 studies with 550 participants. Three studies were conducted in Australia; two in Canada; and one in each of the following: China, the Czech Republic, France, India, the Netherlands, and the USA. One study was conducted in both Israel and Italy. FMT was administered in the form of capsules or suspensions and delivered by mouth, nasoduodenal tube, enema, or colonoscopy. One study delivered FMT by both oral capsules and colonoscopy. Six studies were at overall low risk of bias, while the others had either unclear or high risk of bias. Ten studies with 468 participants, of which nine studies focused on adults and one focused on children, reported induction of clinical remission in people with UC at longest follow-up (range 6 to 12 weeks) and showed that FMT may increase rates of induction of clinical remission in UC compared to control (risk ratio (RR) 1.79, 95% confidence interval (CI) 1.13 to 2.84; low-certainty evidence). Five studies showed that FMT may increase rates of induction of endoscopic remission in UC at longest follow-up (range 8 to 12 weeks); however, the CIs around the summary estimate were wide and included a possible null effect (RR 1.45, 95% CI 0.64 to 3.29; low-certainty evidence). Nine studies with 417 participants showed that FMT may result in little to no difference in rates of any adverse events (RR 0.99, 95% CI 0.85 to 1.16; low-certainty evidence). The evidence was very uncertain about the risk of serious adverse events (RR 1.77, 95% CI 0.88 to 3.55; very low-certainty evidence) and improvement in quality of life (mean difference (MD) 15.34, 95% CI -3.84 to 34.52; very low-certainty evidence) when FMT was used to induce remission in UC. Two studies, of which one also contributed data for induction of remission in active UC, assessed maintenance of remission in people with controlled UC at longest follow-up (range 48 to 56 weeks). The evidence was very uncertain about the use of FMT for maintenance of clinical remission (RR 2.97, 95% CI 0.26 to 34.42; very low-certainty evidence) and endoscopic remission (RR 3.28, 95% CI 0.73 to 14.74; very low-certainty evidence). The evidence was also very uncertain about the risk of serious adverse events, risk of any adverse events, and improvement in quality of life when FMT was used to maintain remission in UC. None of the included studies assessed use of FMT for induction of remission in people with CD. One study with 21 participants reported data on FMT for maintenance of remission in people with CD. The evidence was very uncertain about the use of FMT for maintenance of clinical remission in CD at 24 weeks (RR 1.21, 95% CI 0.36 to 4.14; very low-certainty evidence). The evidence was also very uncertain about the risk of serious or any adverse events when FMT was used to maintain remission in CD. None of the studies reported data on use of FMT for maintenance of endoscopic remission or improvement in quality of life in people with CD. AUTHORS' CONCLUSIONS FMT may increase the proportion of people with active UC who achieve clinical and endoscopic remission. The evidence was very uncertain about whether use of FMT in people with active UC impacted the risk of serious adverse events or improvement in quality of life. The evidence was also very uncertain about the use of FMT for maintenance of remission in people with UC, as well as induction and maintenance of remission in people with CD, and no conclusive statements could be made in this regard. Further studies are needed to address the beneficial effects and safety profile of FMT in adults and children with active UC and CD, as well as its potential to promote longer-term maintenance of remission in UC and CD.
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Affiliation(s)
- Aamer Imdad
- Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Natasha G Pandit
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Muizz Zaman
- Norton College of Medicine, SUNY Upstate Medical University, Syracuse, New York, USA
| | - Nathan Zev Minkoff
- Pediatric Gastroenterology, Hepatology and Nutrition, Valley Children's Hospital, Madera, CA, USA
| | - Emily E Tanner-Smith
- Counseling Psychology and Human Services, University of Oregon, Eugene, Oregon, USA
| | - Oscar G Gomez-Duarte
- Division of Pediatric Infectious Diseases, Department of Pediatrics, University at Buffalo, State University of New York, Buffalo, New York, USA
| | - Sari Acra
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
| | - Maribeth R Nicholson
- Department of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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21
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Abdemalek E, Bose M, Phillips R, Feakins R, Forbes A, Papadia C. The role of biopsy protocol in inflammatory bowel disease: getting the diagnosis right first time. Intern Emerg Med 2023; 18:673-676. [PMID: 36539603 DOI: 10.1007/s11739-022-03175-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 12/06/2022] [Indexed: 12/24/2022]
Affiliation(s)
- Ehab Abdemalek
- Department of Gastroenterology, Princess Alexandra Hospital, Hamstel Rd, Harlow, UK
| | - Monica Bose
- Department of Gastroenterology, Princess Alexandra Hospital, Hamstel Rd, Harlow, UK
| | - Rosemary Phillips
- Department of Gastroenterology, Princess Alexandra Hospital, Hamstel Rd, Harlow, UK
| | - Roger Feakins
- Department of Pathology, University College London, London, UK
| | - Alastair Forbes
- Institute of Clinical Medicine, University of Tartu, Tartu, Estonia
| | - Cinzia Papadia
- Department of Gastroenterology, Whipps Cross University Hospital-Barts Health Trust, Queen Mary University of London, Whipps Cross Road, London, E11 1NR, UK.
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22
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De Craemer AS, Witte T, Lobaton Ortega T, Hoorens A, De Vos M, Cuvelier C, Vastert SJ, Baraliakos X, Van den Bosch F, Elewaut D. Anti-CD74 IgA antibodies show diagnostic potential for axial spondyloarthritis but are not associated with microscopic gut inflammation. Rheumatology (Oxford) 2023; 62:984-990. [PMID: 35781486 DOI: 10.1093/rheumatology/keac384] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2022] [Revised: 06/25/2022] [Accepted: 06/25/2022] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVES Gut inflammation commonly occurs in axial SpA (axSpA), and is linked to disease activity and outcome. Given the role of IgA in mucosal immunity, we explored the association between anti-CD74 IgA antibodies, gut inflammation and axSpA. METHODS Anti-CD74 IgA was measured by ELISA in serum samples of axSpA patients, fulfilling the 2009 Assessment of SpondyloArthritis international Society classification criteria. A group of fibromyalgia (FM) and RA patients served as non-inflammatory and inflammatory controls. Newly diagnosed axSpA patients underwent ileocolonoscopy; mucosal biopsies were histopathologically assessed as normal, acute or chronically inflamed. Optimal anti-CD74 IgA cut-off values were determined with a receiver operating characteristics curve. RESULTS axSpA patients (n = 281) showed higher anti-CD74 IgA levels [mean (s.d.) 18.8 (12.4) U/ml] compared with 100 FM patients [10.9 (5.0) U/ml, P < 0.001] and 34 RA patients [13.7 (9.6) U/ml, P = 0.02]. The area under the receiver operating characteristics curve for diagnosis (axSpA vs FM) was 0.70, providing a sensitivity of 60% and specificity of 87% (cut-off 15 U/ml). Antibody concentrations were not significantly different between axSpA patients with (n = 40) and without (n = 69) gut inflammation (P = 0.83), yielding an area under the receiver operating characteristics curve of 0.51. Anti-CD74 IgA levels were not associated with degree of bone marrow oedema on MRI of the sacroiliac joints, CRP or any other disease-specific feature such as the use of NSAIDs or biological treatment. CONCLUSION Serum anti-CD74 IgA is a potentially useful diagnostic biomarker for axSpA. However, antibody levels do not correlate with any phenotypical feature, including microscopic gut inflammation, suggesting this to be a disease-specific rather than an inflammatory marker.
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Affiliation(s)
- Ann-Sophie De Craemer
- Department of Internal Medicine and Pediatrics, Ghent University
- Department of Rheumatology, Ghent University Hospital, Ghent
- Center for Inflammation Research, Molecular Immunology and Inflammation Unit, VIB-UGent, Zwijnaarde, Belgium
| | - Torsten Witte
- Department of Rheumatology and Clinical Immunology, Medical School Hannover, Hannover, Germany
| | - Triana Lobaton Ortega
- Department of Internal Medicine and Pediatrics, Ghent University
- Department of Gastroenterology
| | - Anne Hoorens
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
| | - Martine De Vos
- Department of Internal Medicine and Pediatrics, Ghent University
- Department of Gastroenterology
| | - Claude Cuvelier
- Department of Pathology, Ghent University Hospital, Ghent, Belgium
| | - Sebastiaan J Vastert
- Department of Pediatric Rheumatology and Immunology, Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, The Netherlands
| | | | - Filip Van den Bosch
- Department of Internal Medicine and Pediatrics, Ghent University
- Department of Rheumatology, Ghent University Hospital, Ghent
- Center for Inflammation Research, Molecular Immunology and Inflammation Unit, VIB-UGent, Zwijnaarde, Belgium
| | - Dirk Elewaut
- Department of Internal Medicine and Pediatrics, Ghent University
- Department of Rheumatology, Ghent University Hospital, Ghent
- Center for Inflammation Research, Molecular Immunology and Inflammation Unit, VIB-UGent, Zwijnaarde, Belgium
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23
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Baidoo N, Sanger GJ, Belai A. Effect of old age on the subpopulations of enteric glial cells in human descending colon. Glia 2023; 71:305-316. [PMID: 36128665 PMCID: PMC10087700 DOI: 10.1002/glia.24272] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 08/22/2022] [Accepted: 08/29/2022] [Indexed: 11/06/2022]
Abstract
Old age is associated with a higher incidence of lower bowel conditions such as constipation. Recent evidence suggest that colonic motility may be influenced by enteric glial cells (EGCs). Little is known about the effect of aging on the subpopulation of EGCs in the human colon. We assessed and compared the pattern of distribution of EGCs in adult and elderly human colon. Human descending colon were obtained from 23 cancer patients comprising of adults (23-63 years; 6 male, 7 female) and elderly (66-81 year; 6 male, 4 female). Specimens were serially-sectioned and immunolabeled with anti-Sox-10, anti-S100 and anti-GFAP for morphometric analysis. Standardized procedures were utilized to ensure unbiased counting and densitometric evaluation of EGCs. The number of Sox-10 immunoreactive (IR) EGCs were unaltered with age in both the myenteric plexus (MP) (respectively, in adult and elderly patients, 1939 ± 82 and 1760 ± 44/mm length; p > .05) and submucosal plexus; there were no apparent differences between adult males and females. The density of S100-IR EGCs declined among the elderly in the circular muscle and within the MP per ganglionic area. In the adult colon, there were more S100-IR EGCs distributed in the circular muscle per unit area than the Taenia coli. There was little or no GFAP-IR EGCs in both adult and elderly colon. We concluded that aging of the human descending colon does not result in a loss of Sox-10-IR EGCs in the MP and SMP but reduces S100-IR EGCs density within the musculature. This alteration in myenteric EGCs density with age may contribute to colonic dysfunction.
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Affiliation(s)
- Nicholas Baidoo
- School of Life and Health Sciences, University of Roehampton, London, UK
| | - Gareth J Sanger
- Blizard Institute, Faculty of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Abi Belai
- School of Life and Health Sciences, University of Roehampton, London, UK
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24
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Pudipeddi A, Fung C, Christensen B, Bryant RV, Subramaniam K, Chetwood J, Paramsothy S, Leong RW. Knowledge and attitudes towards the use of histological assessments in ulcerative colitis by gastroenterologists vs pathologists. World J Gastroenterol 2023; 29:378-389. [PMID: 36687119 PMCID: PMC9846936 DOI: 10.3748/wjg.v29.i2.378] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 11/04/2022] [Accepted: 12/23/2022] [Indexed: 01/06/2023] Open
Abstract
BACKGROUND Histological remission is increasingly accepted as a treatment endpoint in the management of ulcerative colitis (UC). However, the knowledge of histology guidelines and the attitudes towards their use in clinical practice by gastroenterologists and pathologists is unknown.
AIM To evaluate the knowledge of histology guidelines and attitudes towards the use of histology in UC by gastroenterologists and pathologists.
METHODS A prospective, cross-sectional nationwide survey of gastroenterologists and pathologists who analyse UC specimens was conducted. The survey consisted of 34 questions to assess gastroenterologists’ and pathologists’ knowledge (score out of 19) and attitudes towards histological assessment in UC. Survey questions were formulated using the European Crohn’s and Colitis position paper on histopathology and the British Society of Gastroenterology biopsy reporting guidelines. It included knowledge of histological assessment of disease activity and dysplasia, knowledge of histological scoring systems for ulcerative colitis, uptake of histology scoring systems in routine practice, attitudes towards the role of histological activity, and the use of histological activity in clinical scenarios.
RESULTS Of 89 responders (77 gastroenterologists, 12 pathologists), there was almost universal acceptance that histological assessment should form part of UC evaluation [95% gastroenterologists, 92% pathologists]. However, gastroenterologists reported that 92% of their pathologists do not use a histological scoring system. Utilisation of a formal histological scoring system was preferred by 77% of gastroenterologists and 58% of pathologists. Both groups lacked awareness of the Geboes Score, Nancy Index and Robarts Histopathological Index scoring systems with 91%, 87%, and 92% of gastroenterologists respectively; and 83%, 83%, and 92% pathologists respectively, being uncertain of scoring systems’ remission definitions. Histology knowledge score was not significantly different between gastroenterologists and pathologists [9/19 (IQR: 8-11) vs 8/19 (IQR: 7-10), P = 0.54]. Higher knowledge scores were predicted by hospital attending gastroenterologists (P = 0.004), participation in inflammatory bowel disease (IBD) multidisciplinary teams (P = 0.009), and self-declared IBD sub-specialist (P = 0.03).
CONCLUSION Histological remission is a recognised target for both gastroenterologists and pathologists. Despite this, knowledge of histological scoring systems and their utilisation is poor.
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Affiliation(s)
- Aviv Pudipeddi
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
| | - Caroline Fung
- Department of Anatomical Pathology, Concord Repatriation General Hospital, Sydney 2139, Australia
| | - Britt Christensen
- Department of Gastroenterology, Royal Melbourne Hospital, Melbourne 3050, Australia
- Department of Medicine, University of Melbourne, Melbourne 3052, Australia
| | - Robert V Bryant
- Department of Gastroenterology and Hepatology, The Queen Elizabeth Hospital, Adelaide 5011, Australia
| | - Kavitha Subramaniam
- Gastroenterology and Hepatology Unit, Canberra Hospital, Canberra 2605, Australia
- Australian National University Medical School, Australian National University, Canberra 2601, Australia
| | - John Chetwood
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
| | - Sudarshan Paramsothy
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
- Faculty of Medicine and Health Sciences, Macquarie University Hospital, Sydney 2109, Australia
| | - Rupert W Leong
- Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney 2139, Australia
- Faculty of Medicine and Health, Concord Clinical School, University of Sydney, Sydney 2138, Australia
- Faculty of Medicine and Health Sciences, Macquarie University Hospital, Sydney 2109, Australia
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25
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Dysplastic crypts in asymmetric branching found in ulcerative colitis-associated dysplasia. Pathol Res Pract 2022; 240:154178. [DOI: 10.1016/j.prp.2022.154178] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 10/12/2022] [Accepted: 10/14/2022] [Indexed: 11/07/2022]
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26
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The vulnerability of the human taenia coli to alterations in total collagen within the colon of the elderly. Acta Histochem 2022; 124:151958. [DOI: 10.1016/j.acthis.2022.151958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 09/26/2022] [Accepted: 09/27/2022] [Indexed: 11/22/2022]
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27
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Coates E, Wickramasekera N, Barr A, Shackley P, Lee M, Hind D, Probert C, Sebastian S, Totton N, Blackwell S, Bedford H, Dames N, Lobo A. Patient preferences and current practice for adults with steroid-resistant ulcerative colitis: POPSTER mixed-methods study. Health Technol Assess 2022; 26:1-118. [PMID: 36305390 PMCID: PMC9638891 DOI: 10.3310/rhxr5192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
BACKGROUND Corticosteroids are a mainstay of the treatment of moderately severe relapses of ulcerative colitis, yet almost 50% of patients do not respond fully to these and risk prolonged steroid use and side effects. There is a lack of clarity about the definitions of steroid resistance, the optimum choice of treatment, and patient and health-care professional treatment preferences. OBJECTIVES The overall aim of this research was to understand how steroid-resistant ulcerative colitis is managed in adult secondary care and how current practice compares with patient and health-care professional preferences. DESIGN A mixed-methods study, including an online survey, qualitative interviews and discrete choice experiments. SETTING NHS inflammatory bowel disease services in the UK. PARTICIPANTS Adults with ulcerative colitis and health-care professionals treating inflammatory bowel disease. RESULTS We carried out a survey of health-care professionals (n = 168), qualitative interviews with health-care professionals (n = 20) and patients (n = 33), discrete choice experiments with health-care professionals (n = 116) and patients (n = 115), and a multistakeholder workshop (n = 9). The interviews with and survey of health-care professionals showed that most health-care professionals define steroid resistance as an incomplete response to 40 mg per day of prednisolone after 2 weeks. The survey also found that anti-tumour necrosis factor drugs (particularly infliximab) are the most frequently offered drugs across most steroid-resistant (and steroid-dependent) patient scenarios, but they are less frequently offered to thiopurine-naive patients. Patient interviews identified several factors influencing their treatment choices, including effectiveness of treatment, recommendations from health-care professionals, route of administration and side effects. Over time, depending on the severity and duration of symptoms and, crucially, as medical treatment options become exhausted, patients are willing to try alternative treatments and, eventually, to undergo surgery. The discrete choice experiments found that the probability of remission and of side effects strongly influences the treatment choices of both patients and health-care professionals. Patients are less likely to choose a treatment that takes longer to improve symptoms. Health-care professionals are willing to make difficult compromises by tolerating greater safety risks in exchange for therapeutic benefits. The treatments ranked most positively by patients were infliximab and tofacitinib (each preferred by 38% of patients), and the predicted probability of uptake by health-care professionals was greatest for infliximab (62%). LIMITATIONS The survey and the discrete choice experiments with patients and health-care professionals are limited by their relatively small sample sizes. The qualitative studies are subject to selection bias. The timing of the different substudies, both before and during the COVID-19 pandemic, is a potential limitation. CONCLUSIONS We have identified factors influencing treatment decisions for steroid-resistant ulcerative colitis and the characteristics to consider when choosing treatments to evaluate in future randomised controlled trials. The findings may be used to improve discussions between patients and health-care professionals when they review treatment options for steroid-resistant ulcerative colitis. FUTURE WORK This research highlights the need for consensus work to establish an agreed definition of steroid resistance in ulcerative colitis and a greater understanding of the optimal use of tofacitinib and surgery for this patient group. A randomised controlled trial comparing infliximab with tofacitinib is also recommended. FUNDING This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 41. See the NIHR Journals Library website for further project information.
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Affiliation(s)
- Elizabeth Coates
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | | | - Amy Barr
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Phil Shackley
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Matthew Lee
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
| | - Daniel Hind
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | - Christopher Probert
- Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK
| | - Shaji Sebastian
- Hull University Teaching Hospitals NHS Foundation Trust, Hull, UK
| | - Nikki Totton
- School of Health and Related Research, University of Sheffield, Sheffield, UK
| | | | | | | | - Alan Lobo
- Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK
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28
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Deng P, Yao P, Pei C, Li X, Wu J, Zhang S. Significance of diagnosis and prognosis for appendiceal orifice inflammation in ulcerative colitis: a real-world study. BMJ Open 2022; 12:e058973. [PMID: 36180123 PMCID: PMC9528594 DOI: 10.1136/bmjopen-2021-058973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
OBJECTIVE Ulcerative colitis (UC) is a chronic inflammatory disease of the large intestine. At present, the significance of appendiceal orifice inflammation (AOI) in UC prognosis is still controversial. This prospective observational study investigated the importance of AOI in UC diagnosis and prognosis. Additionally, it compared the therapeutic efficacy of treatments in UC patients with or without AOI. DESIGN This study was a prospective, observational, single-centre, real-world study. Patients with AOI were included in the observation group, and patients without AOI were assigned to the control group. All patients were followed up for 1 year; the disease remission and treatment efficacy were re-examined by colonoscopy. In addition, the clinical, endoscopic and pathological features were collected before and after the treatment. RESULTS Patients with endoscopic diffuse inflammatory changes in the distal colorectum accompanied by AOI had a higher positive UC diagnosis rate than those without (96.5% vs 78.0%). Also, AOI had a specificity of 95.2% and a sensitivity of 28.3% for UC diagnosis. However, no difference in the modified Mayo score (p=0.881) or Baron grading was observed between the control and observation groups, indicating that AOI does not affect the treatment outcome of UC patients. CONCLUSION In this study, the observation of AOI improved the UC diagnostic accuracy in patients with diffuse lesions in the distal colorectum. Furthermore, the presence of AOI does not affect the treatment efficacies of UC. TRIAL REGISTRATION NUMBER ChiCTR1800017753.
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Affiliation(s)
- Peng Deng
- Department of Emergency Medicine, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Peng Yao
- Department of Emergency Medicine, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Chao Pei
- Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Xiao Li
- Department of Gastroenterology and Hepatology, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Junchao Wu
- Department of Gastroenterology and Hepatology, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Shu Zhang
- Department of Emergency Medicine, Sichuan University West China Hospital, Chengdu, Sichuan, China
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Liu D, Saikam V, Skrada KA, Merlin D, Iyer SS. Inflammatory bowel disease biomarkers. Med Res Rev 2022; 42:1856-1887. [PMID: 35603998 PMCID: PMC10321231 DOI: 10.1002/med.21893] [Citation(s) in RCA: 67] [Impact Index Per Article: 22.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 11/16/2021] [Accepted: 05/05/2022] [Indexed: 12/16/2022]
Abstract
Inflammatory bowel disease (IBD) is characterized as chronic inflammation in the gastrointestinal tract, which includes two main subtypes, Crohn's disease and ulcerative colitis. Endoscopy combined with biopsy is the most effective way to establish IBD diagnosis and disease management. Imaging techniques have also been developed to monitor IBD. Although effective, the methods are expensive and invasive, which leads to pain and discomfort. Alternative noninvasive biomarkers are being explored as tools for IBD prognosis and disease management. This review focuses on novel biomarkers that have emerged in recent years. These serological biomarkers and microRNAs could potentially be used for disease management in IBD, thereby decreasing patient discomfort and morbidity.
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Affiliation(s)
- Dandan Liu
- Department of Chemistry, 788 Petit Science Center, Georgia State University, Atlanta, Georgia, USA
| | - Varma Saikam
- Department of Chemistry, 788 Petit Science Center, Georgia State University, Atlanta, Georgia, USA
| | - Katie A Skrada
- Department of Chemistry, 788 Petit Science Center, Georgia State University, Atlanta, Georgia, USA
| | - Didier Merlin
- 790 Petit Science Center, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA
- Atlanta Veterans Medical Center, Decatur, Georgia, USA
| | - Suri S Iyer
- Department of Chemistry, 788 Petit Science Center, Georgia State University, Atlanta, Georgia, USA
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30
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Loughrey MB, Wong NACS. Clinical utility of GI pathology data: implications for practising pathologists. J Clin Pathol 2022; 75:519-524. [PMID: 35853655 DOI: 10.1136/jclinpath-2021-207472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 01/25/2022] [Indexed: 11/04/2022]
Abstract
Gastrointestinal (GI) tract pathology represents one of the largest individual specialties within cellular pathology departments globally. As with other specialties, clear communication with clinicians providing primary care for the patient is of utmost importance for optimal management and for appropriate use of resources such as endoscopy. A wide breadth of neoplastic and inflammatory conditions afflicts the GI tract. Here, we aim to illustrate how pathology reporting of GI tract specimens influences patient management and specifically how precise reporting of key parameters in different specimen types and different disease processes can directly impact patient care. We describe the potential clinical relevance of selected pathology data items pertinent to specific conditions and highlight areas of contention with respect to the significance of some pathology features. Recent guidelines are described where a change, for example, in diagnostic criteria for a condition is described, or criteria influencing further management such as endoscopic surveillance. The aim of this review is to focus on the clinical importance of careful written communication between the pathologist and primary clinician, illustrated by selective clinical scenarios involving the upper and lower GI tracts.
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Affiliation(s)
- Maurice B Loughrey
- Department of Cellular Pathology, Royal Victoria Hospital, Belfast Health and Social Care Trust, Belfast, UK .,Centre for Public Health, Queen's University Belfast, School of Medicine, Dentistry and Biomedical Sciences, Belfast, UK
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31
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Baidoo N, Crawley E, Knowles CH, Sanger GJ, Belai A. Total collagen content and distribution is increased in human colon during advancing age. PLoS One 2022; 17:e0269689. [PMID: 35714071 PMCID: PMC9205511 DOI: 10.1371/journal.pone.0269689] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 05/25/2022] [Indexed: 12/26/2022] Open
Abstract
Background The effect of ageing on total collagen content of human colon has been poorly investigated. The aim of this study was to determine if ageing altered total collagen content and distribution in the human colon. Methods Macroscopically normal ascending colon was obtained at surgery from cancer patients (n = 31) without diagnosis of diverticular disease or inflammatory bowel disease. Masson’s trichrome and Picrosirius red stains were employed to identify the total collagen content and distribution within the sublayers of the colonic wall for adult (22–60 years; 6 males, 6 females) and elderly (70 – 91years; 6 males, 4 female) patients. A hydroxyproline assay evaluated the total collagen concentration for adult (30–64 years; 9 male, 6 female) and elderly (66–91 years; 8 male, 8 female) patients. Key results Histological studies showed that the percentage mean intensity of total collagen staining in the mucosa, submucosa and muscularis externa was, respectively, 14(1.9) %, 74(3.2) % and 12(1.5) % in the adult ascending colon. Compared with the adults, the total collagen fibres content was increased in the submucosa (mean intensity; 163.1 ± 11.1 vs. 124.5 ± 7.8; P < 0.05) and muscularis externa (42.5 ± 8.0 vs. 20.6 ± 2.8; P < 0.01) of the elderly patients. There was no change in collagen content of the mucosa. The total collagen concentration was increased in the elderly by 16%. Sex-related differences were not found, and data were combined for analysis. Conclusions Greater total collagen content was found in the submucosa and muscularis externa of the elderly human male and female colon. These changes may contribute to a possible loss of function with ageing.
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Affiliation(s)
- Nicholas Baidoo
- University of Roehampton, School of Life Sciences, London, United Kingdom
| | - Ellie Crawley
- Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Charles H. Knowles
- Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Gareth J. Sanger
- Faculty of Medicine and Dentistry, Blizard Institute, Queen Mary University of London, London, United Kingdom
| | - Abi Belai
- University of Roehampton, School of Life Sciences, London, United Kingdom
- * E-mail:
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Gergely M, Deepak P. Tools for the Diagnosis and Management of Crohn's Disease. Gastroenterol Clin North Am 2022; 51:213-239. [PMID: 35595412 DOI: 10.1016/j.gtc.2021.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Numerous tools have emerged over recent decades to aid in the increasingly complex management of patients with Crohn's disease (CD) beyond endoscopy, including video capsule endoscopy, magnetic resonance enterography, computed tomography enterography, a variety of biomarkers, and even wearable biosensors and smartphone applications. These tools have allowed for a more sophisticated and less invasive complementary approach to the evaluation of disease activity and treatment response in patients with CD. This article details the characteristics, practical application, and limitations of these various modalities and discusses how updated guidelines are now incorporating many of them into a treat-to-target strategy.
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Affiliation(s)
- Maté Gergely
- Division of Gastroenterology, Inflammatory Bowel Diseases Center, Washington University School of Medicine, 600 South Euclid Avenue, Campus Box 8124, Saint Louis, MO 63110, USA
| | - Parakkal Deepak
- Division of Gastroenterology, Inflammatory Bowel Diseases Center, Washington University School of Medicine, 600 South Euclid Avenue, Campus Box 8124, Saint Louis, MO 63110, USA.
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Li Y, Lee AQ, Lu Z, Sun Y, Lu JW, Ren Z, Zhang N, Liu D, Gong Z. Systematic Characterization of the Disruption of Intestine during Liver Tumor Progression in the xmrk Oncogene Transgenic Zebrafish Model. Cells 2022; 11:cells11111810. [PMID: 35681505 PMCID: PMC9180660 DOI: 10.3390/cells11111810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 05/29/2022] [Accepted: 05/30/2022] [Indexed: 01/27/2023] Open
Abstract
The crosstalk between tumors and their local microenvironment has been well studied, whereas the effect of tumors on distant tissues remains understudied. Studying how tumors affect other tissues is important for understanding the systemic effect of tumors and for improving the overall health of cancer patients. In this study, we focused on the changes in the intestine during liver tumor progression, using a previously established liver tumor model through inducible expression of the oncogene xmrk in zebrafish. Progressive disruption of intestinal structure was found in the tumor fish, displaying villus damage, thinning of bowel wall, increase in goblet cell number, decrease in goblet cell size and infiltration of eosinophils, most of which were observed phenotypes of an inflammatory intestine. Intestinal epithelial cell renewal was also disrupted, with decreased cell proliferation and increased cell death. Analysis of intestinal gene expression through RNA-seq suggested deregulation of genes related to intestinal function, epithelial barrier and homeostasis and activation of pathways in inflammation, epithelial mesenchymal transition, extracellular matrix organization, as well as hemostasis. Gene set enrichment analysis showed common gene signatures between the intestine of liver tumor fish and human inflammatory bowel disease, the association of which with cancer has been recently noticed. Overall, this study represented the first systematic characterization of the disruption of intestine under the liver tumor condition and suggested targeting intestinal inflammation as a potential approach for managing cancer cachexia.
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Affiliation(s)
- Yan Li
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (A.Q.L.); (Z.L.); (Y.S.); (J.-W.L.); (Z.R.); (N.Z.)
- Correspondence: (Y.L.); (Z.G.)
| | - Ai Qi Lee
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (A.Q.L.); (Z.L.); (Y.S.); (J.-W.L.); (Z.R.); (N.Z.)
| | - Zhiyuan Lu
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (A.Q.L.); (Z.L.); (Y.S.); (J.-W.L.); (Z.R.); (N.Z.)
- Animal Nutrition Institute, Sichuan Agricultural University, Chengdu 611130, China
| | - Yuxi Sun
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (A.Q.L.); (Z.L.); (Y.S.); (J.-W.L.); (Z.R.); (N.Z.)
- Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China;
| | - Jeng-Wei Lu
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (A.Q.L.); (Z.L.); (Y.S.); (J.-W.L.); (Z.R.); (N.Z.)
| | - Ziheng Ren
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (A.Q.L.); (Z.L.); (Y.S.); (J.-W.L.); (Z.R.); (N.Z.)
| | - Na Zhang
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (A.Q.L.); (Z.L.); (Y.S.); (J.-W.L.); (Z.R.); (N.Z.)
- Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China;
| | - Dong Liu
- Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China;
| | - Zhiyuan Gong
- Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore; (A.Q.L.); (Z.L.); (Y.S.); (J.-W.L.); (Z.R.); (N.Z.)
- Correspondence: (Y.L.); (Z.G.)
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Vessby J, Wisniewski JR, Lindskog C, Eriksson N, Gabrysch K, Zettl K, Wanders A, Carlson M, Rorsman F, Åberg M. AGPAT1 as a Novel Colonic Biomarker for Discriminating Between Ulcerative Colitis With and Without Primary Sclerosing Cholangitis. Clin Transl Gastroenterol 2022; 13:e00486. [PMID: 35363634 PMCID: PMC9132532 DOI: 10.14309/ctg.0000000000000486] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Accepted: 03/15/2022] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Ulcerative colitis (UC) associated with primary sclerosing cholangitis (PSC-UC) is considered a unique inflammatory bowel disease (IBD) entity. PSC diagnosis in an IBD individual entails a significantly higher risk of gastrointestinal cancer; however, biomarkers for identifying patients with UC at risk for PSC are lacking. We, therefore, performed a thorough PSC-UC biomarker study, starting from archived colonic tissue. METHODS Proteins were extracted out of formalin-fixed paraffin-embedded proximal colon samples from PSC-UC (n = 9), UC (n = 7), and healthy controls (n = 7). Patients with IBD were in clinical and histological remission, and all patients with UC had a history of pancolitis. Samples were processed by the multienzyme digestion FASP and subsequently analyzed by liquid chromatography-tandem mass spectrometry. Candidate proteins were replicated in an independent cohort (n: PSC-UC = 16 and UC = 21) and further validated by immunohistochemistry. RESULTS In the discovery step, 7,279 unique proteins were detected. The top 5 most differentiating proteins (PSC-UC vs UC) based on linear regression analysis were selected for replication. Of these, 1-acetylglycerol-3-phosphate O-acyltransferase 1 (AGPAT1) was verified as higher in PSC-UC than UC (P = 0.009) in the replication cohort. A difference on the group level was also confirmed by immunohistochemistry, showing more intense AGPAT1 staining in patients with PSC-UC compared with UC. DISCUSSION We present AGPAT1 as a potential colonic biomarker for differentiating PSC-UC from UC. Our findings have possible implication for future PSC-IBD diagnostics and surveillance.
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Affiliation(s)
- Johan Vessby
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Jacek R. Wisniewski
- Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany;
| | - Cecilia Lindskog
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden;
| | - Niclas Eriksson
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden;
| | - Katja Gabrysch
- Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden;
| | - Katharina Zettl
- Biochemical Proteomics Group, Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany;
| | - Alkwin Wanders
- Department of Pathology, Aalborg University Hospital, Aalborg, Denmark;
| | - Marie Carlson
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Fredrik Rorsman
- Department of Medical Sciences, Gastroenterology Research Group, Uppsala University, Uppsala, Sweden
| | - Mikael Åberg
- Department of Medical Sciences, Clinical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
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Ge C, Lu Y, Shen H, Zhu L. Monitoring of intestinal inflammation and prediction of recurrence in ulcerative colitis. Scand J Gastroenterol 2022; 57:513-524. [PMID: 34994661 DOI: 10.1080/00365521.2021.2022193] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Background and objectives: Ulcerative colitis is a chronic recurrent intestinal inflammatory disease, and its recurrence is difficult to predict. In this review, we summarized the objective indicators that can be used to evaluate intestinal inflammation, the purpose is to better predict the clinical recurrence of UC, formulate individualized treatment plan during remission of UC, and improve the level of diagnosis and treatment of UC.Methods: Based on the search results in the PUBMED database, we explored the accuracy and value of these methods in predicting the clinical recurrence of UC from the following three aspects: endoscopic and histological scores, serum biomarkers and fecal biomarkers.Results: Colonoscopy with biopsy is the gold standard for assessing intestinal inflammation, but it is invasive, inconvenient and expensive. At present, there is no highly sensitive and specific endoscopic or histological score to predict the clinical recurrence of UC. Compared with serum biomarkers, fecal biomarkers have higher sensitivity and specificity because they are in direct contact with the intestine and are closer to the site of intestinal inflammation. Fecal calprotectin is currently the most studied and meaningful fecal biomarker. Lactoferrin and S100A12, as novel biomarkers, have no better performance than FC in predicting the recurrence of UC.Conclusions: FC is currently the most promising predictive marker, but it lacks an accurate cut-off value. Combining patient symptoms, incorporating multiple indicators to construct a UC recurrence prediction model, and formulating individualized treatment plans for high recurrence risk patients will be the focus of UC remission management.
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Affiliation(s)
- Changchang Ge
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Yi Lu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Hong Shen
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Lei Zhu
- Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Krisnuhoni E, Rini Handjari D, Stephanie M, Kencana L, Rahadiani N. Intramucosal Calprotectin Expression in Inflammatory Bowel Disease (IBD) and Non-IBD Colorectal Inflammation. Open Access Maced J Med Sci 2022. [DOI: 10.3889/oamjms.2022.9202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
Abstract
BACKGROUND: Inflammatory bowel disease (IBD) diagnosis remains a challenge accompanied with high numbers of misdiagnosis causing suboptimal management. Tons of trials have been conducted to improve the diagnostic accuracy, one of which is the use of biomarker such as calprotectin. Calprotectin can be detected in tissue (intramucosal) and is becoming a potential marker of IBD.
AIM: This study aims to determine intramucosal calprotectin expression in IBD, non-IBD colitis, and control.
METHODS: This analytic retrospective study included consecutively sampled IBD and non-IBD colitis colorectal biopsy specimens, and control group obtained from Cipto Mangunkusumo Hospital registered from 2017 to 2019. Cases were included in the study if specimens were indicative of IBD and non-IBD clinically and histopathologically and no abnormality were found histopathologically in the control group. Specimens with non-adequate data from the hospital medical records or with missing tissue slides were excluded from the study. Calprotectin immunostaining was conducted to evaluate mean intramucosal calprotectin expression (cell/HPF) in each group.
RESULTS: Most of the samples from IBD and non-IBD group (45 samples each) showed mild active inflammation. Mucosal calprotectin expression in aforementioned groups was higher than that of control group (p < 0.001). Subjects with active inflammation showed higher calprotectin expression compared to those with inactive inflammation (p < 0.001). Calprotectin expression was also related to activity grade.
CONCLUSION: Higher calprotectin expression showed significant association with the presence of inflammation and disease activity. However, the application of intramucosal calprotectin immunohistochemistry test to determine inflammatory etiology (IBD vs. non-IBD) still needs to be further evaluated.
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A Study on Differences between Professional Endoscopists and Gastroenterologists in Endoscopic Detection and Standard Pathological Biopsy of Inflammatory Bowel Diseases. Gastroenterol Res Pract 2022; 2022:7333579. [PMID: 35378864 PMCID: PMC8976660 DOI: 10.1155/2022/7333579] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 01/27/2022] [Accepted: 03/10/2022] [Indexed: 11/24/2022] Open
Abstract
Objective To assess whether professional endoscopists need additional training on inflammatory bowel disease (IBD) diagnosis. Methods This retrospective study was conducted in patients with IBD, including Crohn's disease (CD) and ulcerative colitis (UC), which were diagnosed and treated for the first time in our hospital between January 2005 and December 2020. Doctors including gastroenterologists (group G) and professional endoscopists (group E) participated in the study. The data divided into CD or UC and group G or group E were compared. Results Patients with CD exhibited higher rates of terminal ileal lesions, reexamined colonoscopy within 6 months, and intestinal stenosis than patients with UC (P < 0.001). The positive endoscopic IBD diagnosis rate was significantly higher in group G than in group E (89.6% vs. 74.0%, P < 0.001). In the subgroup analysis for patients with CD, the positive endoscopic IBD diagnosis rate was significantly higher for group G than for group E (81.5% vs. 41.8%, P < 0.001). However, the two groups exhibited no significant difference in the subgroup analysis for patients with UC (94.1% vs. 86.5%, P = 0.060). Group G exhibited a higher rate of terminal ileal intubation (83.1% vs. 65.3%, P < 0.001) and standard pathological biopsy (72.7% vs. 26.0%, P < 0.001) than Group E. Conclusion Professional endoscopists showed lower rates of terminal ileal intubation, positive endoscopic diagnosis, and standard pathological biopsy than gastroenterologists. Hence, additional training on IBD, particularly on CD, must be provided to professional endoscopists to increase their efficiency for terminal ileal intubation and positive endoscopic diagnosis and to enhance their awareness regarding standard biopsy.
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Liu J, Lai X, Bao Y, Xie W, Li Z, Chen J, Li G, Wang T, Huang W, Ma Y, Shi J, Zhao E, Xiang AP, Liu Q, Chen X. Intraperitoneally Delivered Mesenchymal Stem Cells Alleviate Experimental Colitis Through THBS1-Mediated Induction of IL-10-Competent Regulatory B Cells. Front Immunol 2022; 13:853894. [PMID: 35371051 PMCID: PMC8971528 DOI: 10.3389/fimmu.2022.853894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 02/21/2022] [Indexed: 11/25/2022] Open
Abstract
Mesenchymal stem cells (MSCs) show promising therapeutic potential in treating inflammatory bowel disease (IBD), and intraperitoneal delivery of MSCs have become a more effective route for IBD treatment. However, the underlying mechanisms are still poorly understood. Here, we found that intraperitoneally delivered MSCs significantly alleviated experimental colitis. Depletion of peritoneal B cells, but not macrophages, clearly impaired the therapeutic effects of MSCs. Intraperitoneally delivered MSCs improved IBD likely by boosting the IL-10-producing B cells in the peritoneal cavity, and a single intraperitoneal injection of MSCs could significantly prevent disease severity in a recurrent mouse colitis model, with lower proinflammation cytokines and high level of IL-10. The gene expression profile revealed that thrombospondin-1 (THBS1) was dramatically upregulated in MSCs after coculture with peritoneal lavage fluid from colitis mice. Knockout of THBS1 expression in MSCs abolished their therapeutic effects in colitis and the induction of IL-10-producing B cells. Mechanistically, THBS1 modulates the activation of transforming growth factor-β (TGF-β), which combines with TGF-β receptors on B cells and contributes to IL-10 production. Blocking the interaction between THBS1 and latent TGF-β or inhibiting TGF-β receptors (TGF-βR) significantly reversed the THBS1-mediated induction of IL-10-producing B cells and the therapeutic effects on colitis. Collectively, our study revealed that intraperitoneally delivered MSCs secreted THBS1 to boost IL-10+Bregs and control the progression and recurrence of colitis, providing new insight for the prevention and treatment of IBD.
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Affiliation(s)
- Jialing Liu
- The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Xingqiang Lai
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
- Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yingying Bao
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Wenfeng Xie
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Zhishan Li
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Jieying Chen
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Gang Li
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Tao Wang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Weijun Huang
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Yuanchen Ma
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Jiahao Shi
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Erming Zhao
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
| | - Andy Peng Xiang
- The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Xiaoyong Chen, ; Qiuli Liu, ; Andy Peng Xiang,
| | - Qiuli Liu
- The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Xiaoyong Chen, ; Qiuli Liu, ; Andy Peng Xiang,
| | - Xiaoyong Chen
- The Biotherapy Center, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
- Center for Stem Cell Biology and Tissue Engineering, Key Laboratory for Stem Cells and Tissue Engineering, Ministry of Education, Sun Yat-sen University, Guangzhou, China
- Department of Pathophysiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
- *Correspondence: Xiaoyong Chen, ; Qiuli Liu, ; Andy Peng Xiang,
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Feakins R, Torres J, Borralho-Nunes P, Burisch J, Cúrdia Gonçalves T, De Ridder L, Driessen A, Lobatón T, Menchén L, Mookhoek A, Noor N, Svrcek M, Villanacci V, Zidar N, Tripathi M. ECCO Topical Review on Clinicopathological Spectrum and Differential Diagnosis of Inflammatory Bowel Disease. J Crohns Colitis 2022; 16:343-368. [PMID: 34346490 DOI: 10.1093/ecco-jcc/jjab141] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Many diseases can imitate inflammatory bowel disease [IBD] clinically and pathologically. This review outlines the differential diagnosis of IBD and discusses morphological pointers and ancillary techniques that assist with the distinction between IBD and its mimics. METHODS European Crohn's and Colitis Organisation [ECCO] Topical Reviews are the result of an expert consensus. For this review, ECCO announced an open call to its members and formed three working groups [WGs] to study clinical aspects, pathological considerations, and the value of ancillary techniques. All WGs performed a systematic literature search. RESULTS Each WG produced a draft text and drew up provisional Current Practice Position [CPP] statements that highlighted the most important conclusions. Discussions and a preliminary voting round took place, with subsequent revision of CPP statements and text and a further meeting to agree on final statements. CONCLUSIONS Clinicians and pathologists encounter a wide variety of mimics of IBD, including infection, drug-induced disease, vascular disorders, diverticular disease, diversion proctocolitis, radiation damage, and immune disorders. Reliable distinction requires a multidisciplinary approach.
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Affiliation(s)
- Roger Feakins
- Department of Cellular Pathology, Royal Free Hospital, London, and University College London, UK
| | - Joana Torres
- Department of Gastroenterology, Hospital Beatriz Ângelo, Loures, Portugal
| | - Paula Borralho-Nunes
- Department of Pathology, Hospital Cuf Descobertas, Lisboa and Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal
| | - Johan Burisch
- Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Tiago Cúrdia Gonçalves
- Department of Gastroenterology, Hospital da Senhora da Oliveira, Guimarães, Portugal.,School of Medicine, University of Minho, Braga/Guimarães, Portugal.,ICVS/3B's-PT Government Associate Laboratory, Braga/Guimarães, Portugal
| | - Lissy De Ridder
- Department of Paediatric Gastroenterology, Erasmus MC Sophia Children's Hospital, University Medical Center Rotterdam, The Netherlands
| | - Ann Driessen
- Department of Pathology, University Hospital Antwerp, University Antwerp, Edegem, Belgium
| | - Triana Lobatón
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Luis Menchén
- Department of Digestive System Medicine, Hospital General Universitario-Insitituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.,Department of Medicine, Universidad Complutense, Madrid, Spain.,Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas [CIBEREHD], Madrid, Spain
| | - Aart Mookhoek
- Department of Pathology, Amsterdam UMC, Amsterdam, The Netherlands
| | - Nurulamin Noor
- Department of Gastroenterology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust, Cambridge, UK
| | - Magali Svrcek
- Department of Pathology, Sorbonne Université, AP-HP, Saint-Antoine Hospital, Paris, France
| | - Vincenzo Villanacci
- Department of Histopathology, Spedali Civili and University of Brescia, Brescia, Italy
| | - Nina Zidar
- Institute of Pathology, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Monika Tripathi
- Department of Histopathology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
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40
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Rubio CA, Schmidt PT, Lang-Schwarz C, Vieth M. Branching crypts in inflammatory bowel disease revisited. J Gastroenterol Hepatol 2022; 37:440-445. [PMID: 34750862 DOI: 10.1111/jgh.15734] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Accepted: 10/26/2021] [Indexed: 12/13/2022]
Abstract
Histologic sections from patients with inflammatory bowel disease (IBD) usually exhibit crypts with architectural distortions and branching crypts. It has been postulated that crypt branching should be assessed only in well-oriented, upright crypts. However, those crypts are mostly found in sections from colectomy specimens and colon mucosectomies. Sections from endoscopic biopsies are fortuitously cut in a horizontal plane, a procedure mostly revealing cross-cut crypt rings. In endoscopic biopsies from UC patients we previously detected cross-cut crypts heralding the crest domain of branching crypts. Recently, the scrutiny of biopsies from IBD patients revealed that branching-crest domains concurred either with crypts in symmetric branching, typified by twin, amalgamating back-to-back isometrics crypt-rings, or with crypts in asymmetric branching, characterized by ≥2 amalgamating anisometric crypt-rings; both symmetric and asymmetric branching-crest domains were encased by a thin muscularis mucosae. Quantitative studies in biopsies from Swedish and German patients with IBD showed that crypts in asymmetric branching outnumbered those in symmetric branching. Because crypt-branching seldom occurs in the normal colon in adults and considering that colon crypts typically divide once or twice during a lifetime, the accruing of asymmetric branching crypts in IBD biopsies emerges as a significant histologic parameter. Although the biological significance of asymmetric crypt-branching in IBD remains at present elusive, their occurrence deserves to be further investigated. The future policy will be to include in our pathologic reports, the number of crypts in asymmetric branching, in order to monitor their frequency in prospective surveillance biopsies in patients with IBD.
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Affiliation(s)
- Carlos A Rubio
- Department of Pathology, Karolinska Institute and University Hospital, Stockholm, Sweden
| | - Peter T Schmidt
- Department of Medicine, Karolinska Institute and Ersta Hospital, Stockholm, Sweden
| | | | - Michael Vieth
- Friedrich-Alexander-University Erlangen-Nuremberg, Bayreuth, Germany
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41
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Núñez F P, Quera R, Rubin DT. Endoscopic colorectal cancer surveillance in inflammatory bowel disease: Considerations that we must not forget. World J Gastrointest Endosc 2022; 14:85-95. [PMID: 35316980 PMCID: PMC8908328 DOI: 10.4253/wjge.v14.i2.85] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 08/02/2021] [Accepted: 01/23/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic immune-mediated inflammatory disease that primarily affects the gastrointestinal tract and is characterized by periods of activity and remission. The inflammatory activity of the disease involving the colon and rectum increases the risk of colorectal cancer (CRC) over the years. Although prevention strategies are evolving, regular surveillance for early detection of neoplasia as a secondary prevention strategy is paramount in the care of IBD patients. In this review article, we discuss the current evidence of the risks of developing CRC and evaluate the best available strategies for screening and surveillance, as well as future opportunities for cancer prevention.
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Affiliation(s)
- Paulina Núñez F
- Universidad de los Andes, Digestive Disease Center, Inflammatory Bowel Disease Program, Clinica, Santiago 7620157, RM, Chile
- Department of Gastroenterology, Hospital San Juan de Dios. Universidad de Chile, Santiago 7701230, RM, Chile
| | - Rodrigo Quera
- Universidad de los Andes, Digestive Disease Center, Inflammatory Bowel Disease Program, Clinica, Santiago 7620157, RM, Chile
| | - David T Rubin
- Medicine Inflammatory Bowel Disease Center, University of Chicago, Chicago, IL 60637, United States
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42
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Sampling and Reporting of Inflammatory Bowel Disease. Adv Anat Pathol 2022; 29:25-36. [PMID: 34879036 DOI: 10.1097/pap.0000000000000318] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/04/2022]
Abstract
Pathologists have an important and expanding role in the diagnosis and management of inflammatory bowel disease. This role includes the initial diagnosis of the disease, assessment of the response to treatment and the identification of short-term complications such as cytomegalovirus infection and long-term complications such as dysplasia. Furthermore, the assessment of resection specimens for complication of disease is important to determining the risk of subsequent disease or inflammation within an ileal pouch. Adequate sampling of the disease at endoscopy and from the surgical resection specimen is vital to determining the ultimate information that can be provided by the pathologist. This sampling is determined by the clinical scenario. Similarly, a standardized approach to reporting and synthesizing the histologic findings will improve patient management. This is best exemplified by the increasing interest in histologic activity indices, such as the Nancy index in ulcerative colitis, and in the standardized reporting for inflammatory bowel disease dysplasia recommended by the SCENIC international consensus.
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Rezazadeh Ardabili A, Goudkade D, Wintjens D, Romberg-Camps M, Winkens B, Pierik M, Grabsch HI, Jonkers D. Histopathological Features in Colonic Biopsies at Diagnosis Predict Long-term Disease Course in Patients with Crohn's Disease. J Crohns Colitis 2021; 15:1885-1897. [PMID: 33987670 PMCID: PMC8575048 DOI: 10.1093/ecco-jcc/jjab087] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
BACKGROUND AND AIMS Crohn's disease [CD] is characterised by a heterogeneous disease course. Patient stratification at diagnosis using clinical, serological, or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features to discriminate between a long-term mild and severe disease course. METHODS Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis were reviewed by two gastrointestinal pathologists after developing a standardised form comprising 15 histopathological features. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristic [ROC] curves. Models were internally validated using bootstrapping to obtain optimism-corrected performance estimates. RESULTS In total, 817 biopsies from 137 patients [64 mild, 73 severe cases] were included. Using clinical baseline characteristics, disease course could only moderately be predicted (area under receiver operating characteristic curve [AUROC]: 0.738 [optimism 0.018], 95% confidence interval [CI] 0.65-0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic biopsies a combination of [1] basal plasmacytosis, [2] severe lymphocyte infiltration in lamina propria, [3] Paneth cell metaplasia, and [4] absence of ulcers were identified and resulted in significantly better prediction of a severe course (AUROC: 0.883 [optimism 0.033], 95% CI 0.82-0.94, sensitivity 80.4%, specificity 84.2%). CONCLUSIONS In this first study investigating the additive predictive value of histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improving stratification and facilitating clinical decision making.
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Affiliation(s)
- Ashkan Rezazadeh Ardabili
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands
- School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
- Corresponding author: Ashkan Rezazadeh Ardabili, MD, Department of Internal Medicine, Division of Gastroenterology and Hepatology, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Postbox 5800, 6202 AZ, Maastricht, The Netherlands. Tel.: 0031-43-3884203; fax: 0031-43-3875006;
| | - Danny Goudkade
- Department of Pathology, Zuyderland Medical Centre, Geleen, The Netherlands
| | - Dion Wintjens
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands
- School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Mariëlle Romberg-Camps
- Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine, Zuyderland Medical Centre, Sittard-Geleen, The Netherlands
| | - Bjorn Winkens
- Department of Methodology and Statistics, Care and Public Health Research Institute, Maastricht University, Maastricht, The Netherlands
| | - Marie Pierik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands
- School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
| | - Heike I Grabsch
- Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands
- Division of Pathology & Data Analytics, Leeds Institute of Medical Research at St James’s, University of Leeds, Leeds, UK
| | - Daisy Jonkers
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Center+, Maastricht, The Netherlands
- School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, The Netherlands
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44
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Wyatt NJ, Speight RA, Stewart CJ, Kirby JA, Lamb CA. Targeting Leukocyte Trafficking in Inflammatory Bowel Disease. BioDrugs 2021; 35:473-503. [PMID: 34613592 DOI: 10.1007/s40259-021-00496-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/04/2021] [Indexed: 12/11/2022]
Abstract
In the last two decades, understanding of inflammatory bowel disease (IBD) immunopathogenesis has expanded considerably. Histopathological examination of the intestinal mucosa in IBD demonstrates the presence of a chronic inflammatory cell infiltrate. Research has focused on identifying mechanisms of immune cell trafficking to the gastrointestinal tract that may represent effective gut-selective targets for IBD therapy whilst avoiding systemic immunosuppression that may be associated with off-target adverse effects such as infection and malignancy. Integrins are cell surface receptors that can bind to cellular adhesion molecules to mediate both leukocyte homing and retention. In 2014, Vedolizumab (Entyvio®) was the first anti-integrin (anti-α4ß7 monoclonal antibody) treatment to be approved for use in IBD. Several other anti-integrin therapies are currently in advanced stages of development, including novel orally administered small-molecule drugs. Drugs targeting alternative trafficking mechanisms such as mucosal addressin cellular adhesion molecule-1 and sphingosine-1-phosphate receptors are also being evaluated. Here, we summarise key established and emerging therapies targeting leukocyte trafficking that may play an important role in realising the goal of stratified precision medicine in IBD care.
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Affiliation(s)
- Nicola J Wyatt
- Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.,Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK
| | - R Alexander Speight
- Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.,Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK
| | - Christopher J Stewart
- Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
| | - John A Kirby
- Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
| | - Christopher A Lamb
- Faculty of Medical Sciences, Translational & Clinical Research Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK. .,Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, NE1 4LP, UK.
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45
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Gupta A, Yu A, Peyrin-Biroulet L, Ananthakrishnan AN. Treat to Target: The Role of Histologic Healing in Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2021; 19:1800-1813.e4. [PMID: 33010406 DOI: 10.1016/j.cgh.2020.09.046] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/17/2020] [Accepted: 09/20/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Endoscopic remission is a recognized therapeutic endpoint in inflammatory bowel disease (IBD; Crohn's disease (CD), ulcerative colitis (UC)). The impact of persistent histologic activity on long-term outcomes is less clear and limited by small studies. METHODS We performed a systematic search of PubMed and Embase to identify eligible studies examining the association between histologic activity and relapse in patients with CD or UC in endoscopic remission. Studies were pooled together using random effects meta-analysis per the DerSimonian and Laird inverse variance method. The impact of different histologic scales, cut-offs, and individual features were examined. FINDINGS Our meta-analysis included 28 studies contributing 2,806 patients (2677 UC; 129 CD). In UC, histologically active disease was associated with an overall increased risk of relapse (OR, 2.41; 95% CI, 1.91-3.04), with a similar effect noted in the subgroup with endoscopic Mayo endoscopic score of 0 vs 0 or 1. More rigorous Geboes cut-offs demonstrated numerically stronger impact on relapse rates-Geboes <3.1 (OR, 2.40; 95% CI, 1.57-3.65), Geboes <2.1 (OR, 3.91; 95% CI, 2.21-6.91) and Geboes 0 (OR, 7.40; 95% CI, 2.00-18.27). Among individual histologic features, basal plasmacytosis (OR, 1.94), neutrophilic infiltrations (OR, 2.30), mucin depletion (OR, 2.05), and crypt architectural irregularities (OR, 2.22) predicted relapse. There was no association between histologic activity and relapse in CD. CONCLUSIONS In patients with UC in endoscopic remission, persistent histologic activity is associated with higher rates of relapse. Greater degree of normalization may have a stronger impact.
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Affiliation(s)
- Akshita Gupta
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Amy Yu
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandoeuvre-les-Nancy, France; French Institute of Health and Medical Research U1256 NGERE, University of Lorraine, Vandoeuvre-les-Nancy, France
| | - Ashwin N Ananthakrishnan
- Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
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46
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Adamina M, Feakins R, Iacucci M, Spinelli A, Cannatelli R, D'Hoore A, Driessen A, Katsanos K, Mookhoek A, Myrelid P, Pellino G, Peros G, Tontini GE, Tripathi M, Yanai H, Svrcek M. ECCO Topical Review Optimising Reporting in Surgery, Endoscopy, and Histopathology. J Crohns Colitis 2021; 15:1089-1105. [PMID: 33428711 DOI: 10.1093/ecco-jcc/jjab011] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS Diagnosis and management of inflammatory bowel diseases [IBD] requires a lifelong multidisciplinary approach. The quality of medical reporting is crucial in this context. The present topical review addresses the need for optimised reporting in endoscopy, surgery, and histopathology. METHODS A consensus expert panel consisting of gastroenterologists, surgeons, and pathologists, convened by the European Crohn's and Colitis Organisation, performed a systematic literature review. The following topics were covered: in endoscopy: [i] general IBD endoscopy; [ii] disease activity and surveillance; [iii] endoscopy treatment in IBD; in surgery: [iv] medical history with surgical relevance, surgical indication, and strategy; [v] operative approach; [vi] intraoperative disease description; [vii] operative steps; in pathology: [viii] macroscopic assessment and interpretation of resection specimens; [ix] IBD histology, including biopsies, surgical resections, and neoplasia; [x] IBD histology conclusion and report. Statements were developed using a Delphi methodology incorporating two consecutive rounds. Current practice positions were set when ≥ 80% of participants agreed on a recommendation. RESULTS Thirty practice positions established a standard terminology for optimal reporting in endoscopy, surgery, and histopathology. Assessment of disease activity, surveillance recommendations, advice to surgeons for operative indication and strategies, including margins and extent of resection, and diagnostic criteria of IBD, as well as guidance for the interpretation of dysplasia and cancer, were handled. A standardised report including a core set of items to include in each specialty report, was defined. CONCLUSIONS Interdisciplinary high-quality care requires thorough and standardised reporting across specialties. This topical review offers an actionable framework and practice recommendations to optimise reporting in endoscopy, surgery, and histopathology.
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Affiliation(s)
- Michel Adamina
- Department of Surgery, Cantonal Hospital Winterthur, Winterthur, Switzerland
- Faculty of Medicine, University of Basel, Basel, Switzerland
| | - Roger Feakins
- Department of Cellular Pathology, Royal Free Hospital, London, UK
| | - Marietta Iacucci
- Institute of Immunology and Immunotherapy, NIHR Biomedical Research Centre, University of Birmingham, UK
- Division of Gastroenterology, University Hospitals Birmingham NHS Trust, UK
| | - Antonino Spinelli
- Division of Colon and Rectal Surgery, Humanitas Clinical and Research Center, Rozzano,Italy
- Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Rosanna Cannatelli
- Institute of Translational Medicine, University of Birmingham, Birmingham, UK
- Gastroenterology Unit, Spedali Civili di Brescia, Brescia, Italy
| | - André D'Hoore
- Department of Abdominal Surgery, University Hospital Leuven, Leuven, Belgium
| | - Ann Driessen
- Department of Pathology, University Hospital Antwerp, University Antwerp, Edegem, Belgium
| | - Konstantinos Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Aart Mookhoek
- Department of Pathology, Amsterdam UMC, Amsterdam, The Netherlands
| | - Pär Myrelid
- Department of Surgery, and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Gianluca Pellino
- Department of Advanced Medical and Surgical Sciences, Universitá degli Studi della Campania 'Luigi Vanvitelli', Naples, Italy
- Colorectal Unit, Vall d'Hebron University Hospital, Barcelona, Spain
| | - Georgios Peros
- Department of Surgery, Cantonal Hospital of Winterthur, Winterthur, Switerland; Division of Colon and Rectal Surgery, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Gian Eugenio Tontini
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Monika Tripathi
- Department of Histopathology, Cambridge Biomedical Campus, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
| | - Henit Yanai
- Division of Gastroenterology, IBD Center, Rabin Medical Center, Petah Tikva, Israel
| | - Magali Svrcek
- Department of Pathology, Sorbonne Université, AP-HP, Saint-Antoine hospital, Paris, France
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Abstract
A previously well 37-year-old woman attended the emergency assessment unit with symptoms of lethargy, breathlessness and peripheral oedema, whereby initial basic investigations revealed an iron deficiency anaemia and serum hypoalbuminaemia. The patient subsequently had multiple admissions to secondary care over a 2-year period due to worsening peripheral and central oedema. Investigations ruled out non-gastrointestinal causes of serum hypoalbuminaemia, such as renal, cardiac and hepatic failures. Gastrointestinal investigations later revealed raised faecal alpha-1 antitrypsin and small bowel ulceration on capsule endoscopy, with a histological diagnosis of Crohn's disease made after a small bowel wedge resection. This case describes the unusual presentation of Crohn's disease displaying symptoms primarily of protein-losing enteropathy, an uncommon and under-recognised consequence of inflammatory bowel disease. A review of current literature and the underlying pathophysiology for this rare condition are discussed, particularly in relation to Crohn's disease.
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Affiliation(s)
- Kate Edwards
- Gastroenterology, Nevill Hall Hospital, Abergavenny, UK
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48
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Zysset D, Montani M, Spalinger J, Schibli S, Zlobec I, Mueller C, Sokollik C. Molecular and Histological Profiling Reveals an Innate-Shaped Immune Microenvironment in Solitary Juvenile Polyps. Clin Transl Gastroenterol 2021; 12:e00361. [PMID: 34060497 PMCID: PMC8162518 DOI: 10.14309/ctg.0000000000000361] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 04/27/2021] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION Solitary juvenile polyps (JP) are characterized by a benign disease course with low recurrence rate but present with signs of intestinal inflammation. To better understand the underlying pathogenesis, we performed histological and molecular evaluation targeting distinct immune mechanisms. METHODS Pediatric patients with JP (n = 12), with treatment-naïve inflammatory bowel disease (IBD; [n = 41]) as inflammatory control, and non-IBD controls (n = 14) were investigated. For a comparative analysis of infiltrating immune cells, a next-generation tissue microarray of biopsies was assembled, immunostained, and scored. Targeted transcriptional profiling was performed using a customized immunology panel. RESULTS In JP, a predominant accumulation of neutrophils and eosinophils was observed. RNA expression profiles revealed increased levels of CXCL8, CXCL5, and CCL11 transcripts in JP, indicating an enhanced recruitment of neutrophils and eosinophils. Moreover, messenger RNA levels of the proinflammatory cytokine IL1b and the inflammation-amplifying receptor TREM1 were higher in JP, whereas we could not find signs of a functionally polarized Tcell response in JP when compared with IBD. DISCUSSION Patients with JP and patients with treatment-naïve IBD have distinct cell infiltrates during active disease. The ample presence of eosinophils in JP supports neutrophil accumulation, which is responsible for the elevated release of calprotectin. Intriguingly, however, we were not able to identify a functionally polarized T-cell response in JP, which indicates that during the acute onset of inflammation in JP, a potent adaptive immune memory is not established. This may explain the low reoccurrence rate of JP.
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Affiliation(s)
- Daniel Zysset
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - Matteo Montani
- Institute of Pathology, University of Bern, Bern, Switzerland
| | | | - Susanne Schibli
- Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital, Inselspital, University of Bern, Switzerland
| | - Inti Zlobec
- Institute of Pathology, University of Bern, Bern, Switzerland
| | | | - Christiane Sokollik
- Pediatric Gastroenterology, Hepatology, and Nutrition, Children's Hospital, Inselspital, University of Bern, Switzerland
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Morey-Matamalas A, Denk D, Silina A, Stidworthy MF, Mätz-Rensing K, Bleyer M, Baiker K. Histopathological Characterization of Colitis in Captive Western Lowland Gorillas (Gorilla gorilla ssp gorilla). J Comp Pathol 2021; 185:108-117. [PMID: 34119227 DOI: 10.1016/j.jcpa.2021.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2020] [Revised: 02/11/2021] [Accepted: 04/16/2021] [Indexed: 11/16/2022]
Abstract
In captive gorillas, ulcerative colitis is an important cause of morbidity and mortality with no established definitive aetiopathogenesis. The aim of the study was to characterize histopathologically colonic lesions in captive western lowland gorillas (Gorilla gorilla ssp gorilla) and to apply the Nancy index, a disease activity scoring system for ulcerative colitis in humans. Colon samples from 21 animals were evaluated on the basis of histopathological characteristics for the diagnosis of inflammatory bowel disease in humans and divided into acute or chronic changes. The most common acute changes included the presence of neutrophils in the lamina propria (17/18; 94%), mucosal and submucosal oedema (12/18; 67%) and crypt abscesses (8/18; 44%). The most common chronic changes were lamina proprial lymphoplasmacytic infiltrates (17/18; 94%) and crypt dilation or distortion (6/18; 33%). Based on the Nancy index, 4/21 (19%) cases were grade 4 (the highest grade), 2/21 (10%) were grade 3, 11/21 (52%) were grade 2 and 4/21 (19%) cases were grade 0. The colonic changes were comparable to the acute phase of ulcerative colitis in humans. No unifying aetiopathogenesis could be identified. The Nancy index proved to be a valuable tool for the standardization of disease grading and established a basis for future studies of gorilla colitis.
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Affiliation(s)
- Antonia Morey-Matamalas
- Veterinary Pathology Service, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, UK.
| | - Daniela Denk
- IZVG Pathology, International Zoo Veterinary Group, Keighley, UK
| | - Anna Silina
- Veterinary Pathology Service, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, UK
| | | | - Kerstin Mätz-Rensing
- German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany
| | - Martina Bleyer
- German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany
| | - Kerstin Baiker
- Veterinary Pathology Service, School of Veterinary Medicine and Science, University of Nottingham, Sutton Bonington Campus, UK
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de Frias Gomes CG, de Almeida ASR, Mendes CCL, Ellul P, Burisch J, Buhagiar T, Attard A, Lo B, Ungaro RC, da Silva Morão BT, Gouveia CF, de Carvalho e Branco JMD, Rodrigues JMMP, Teixeira C, Dias de Castro MFF, Nunes GFD, Brito M, de Sousa Antunes MC, Borralho Nunes PMFB, da Silva Torres JMT. Histological Inflammation in the Endoscopically Uninflamed Mucosa is Associated With Worse Outcomes in Limited Ulcerative Colitis. Inflamm Bowel Dis 2021; 28:350-357. [PMID: 33999195 PMCID: PMC8889288 DOI: 10.1093/ibd/izab069] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND The Montreal classification categorizes patients with ulcerative colitis (UC) based on their macroscopic disease extent. Independent of endoscopic extent, biopsies through all colonic segments should be retrieved during index colonoscopy. However, the prognostic value of histological inflammation at diagnosis in the inflamed and uninflamed regions of the colon has never been assessed. METHODS This was a multicenter retrospective cohort study of newly diagnosed patients with treatment-naïve proctitis and left-sided UC. Biopsies from at least 2 colonic segments (endoscopically inflamed and uninflamed mucosa) were retrieved and reviewed by 2 pathologists. Histological features in the endoscopically inflamed and uninflamed mucosa were scored using the Nancy score. The primary outcomes were disease complications (proximal disease extension, need for hospitalization or colectomy) and higher therapeutic requirements (need for steroids or for therapy escalation). RESULTS Overall, 93 treatment-naïve patients were included, with a median follow-up of 44 months (range, 2-329). The prevalence of any histological inflammation above the endoscopic margin was 71%. Proximal disease extension was more frequent in patients with histological inflammation in the endoscopically uninflamed mucosa at diagnosis (21.5% vs 3.4%, P = 0.04). Histological involvement above the endoscopic margin was the only predictor associated with an earlier need for therapy escalation (adjusted hazard ratio, 3.69; 95% confidence interval, 1.05-13.0); P = 0.04) and disease complications (adjusted hazard ratio, 4.79; 95% confidence interval, 1.10-20.9; P = 0.04). CONCLUSIONS The presence of histological inflammation in the endoscopically uninflamed mucosa at the time of diagnosis was associated with worse outcomes in limited UC.
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Affiliation(s)
| | | | | | | | - Johan Burisch
- Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | | | | | - Bobby Lo
- Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark
| | - Ryan C Ungaro
- The Dr. Henry Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | | | | | | | | | - Cristina Teixeira
- Gastroenterology Division, Centro Hospitalar de Setúbal, Setúbal, Portugal
| | | | | | - Mariana Brito
- Gastroenterology Division, Hospital Garcia de Orta, Almada, Portugal
| | | | | | - Joana Maria Tinoco da Silva Torres
- Gastroenterology Division, Hospital Beatriz Ângelo, Loures, Portugal,Address correspondence to: Joana Torres, MD, PhD, Gastroenterology Division, Hospital Beatriz Ângelo, Avenida Carlos Teixeira, 3 2674-514 Loures, Portugal ()
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